Resources to support addiction counselors: A qualitative investigation

Background and Objective: Counselors have high burnout rates caused by demanding workloads. The objective of this research was to identify possible resources which could make a substance use counselors’ job easier. Methods: This qualitative study collected its information through interviews done over the phone or in person. Results: The counselors answers identified they feel overwhelmed and often have to multitask, which creates feelings of stress. Conclusions: A resource guide of group activities could help ease the stress caused by having to multitask.SMURSUNY EmpireN/

A category theoretic bridge from classical error correction to quantum error correction

Both the category Set of sets and functions as well as the category EVect of Euclidean vector spaces and their linear maps form monoidal categories under the Cartesian product and the tensor product, respectively. We categorically model classical computing within a full monoidal subcategory of Set, and similarly quantum computing within a full monoidal subcategory of EVect. The free functor offers a map expressing how all classical computing algorithms can be functorially mapped to a corresponding quantum algorithm. Error correction codes are included in this model using natural transformations and shown by examples, i.e Hamming codes and Toric codes, to maintain the objects and morphisms of their respective categories. Keywords: mathematics, math, computer science, linear algebra, Deustch-Josza algorithm, Toric codes, Hamming codes, Three-Bit Repetition code, Three-Qubit Repetition code, category theory, quan-tum computing, classical computing, error correction, classical error correction, quantum error correction, free functor, monoidal category, categoryNASUNY College at New PaltzHonorsN/AGlass, CheyneSullivan, Patrici

Nanobody development for therapeutically targeting Vacuolar H+-ATPases

The vacuolar H+-ATPase (V-ATPase, V1Vo) is a dedicated proton pump that is highly conserved amongst eukaryotes, and is necessary for pH homeostasis within subcellular compartments. The V-ATPase consists of two subcomplexes: the soluble V1 responsible for hydrolyzing ATP, and the membrane integral Vo responsible for proton translocation across membranes. V1 and Vo are each comprised of multiple subunits, A3B3CDE3FG3 and ac8c'c"def Voa1 respectively. Many basic cellular functions depend on the differential pH gradient across cellular membranes to operate properly, making regulation of V-ATPases through "reversible disassembly" immensely important. Global loss of V-ATPase activity is lethal to all mammalian cell types, while aberrant activity and incorrectly localized V-ATPase results in various disease states. Current therapeutics struggle to target specific V-ATPase populations, and as a potential solution to this problem we generated 94 nanobody clones against the yeast nanodisc reconstituted Vo (VoND). Nanobodies (Nbs) are the small 15 kDa VHH domain isolated from heavy-chain only antibodies that are known for their high specificity. In this dissertation we describe the characterization of three α-yeast VoND Nbs, N27, N125, and N2149. Using an ATPase assay, we found that N27, but not N125 or N21149, fully inhibited the activity of assembled V-ATPase. Contrastingly, N2149, but not N27 or N125, was found to inhibit the assembly of the two subcomplexes. BLI was used to identify the binding affinity of each Nb, with affinities being observed in the nM-pM range. High-resolution structures obtained from cryoEM revealed the subunit specificity of each Nb, with N27 and N125 found to bind the c-ring in different stoichiometries, and N2149 found to bind the d subunit. Furthermore, we determined that N125 has cross affinity for the human enzyme. Overall, this study provides evidence that novel nanobody mediated inhibition of assembly or activity of V-ATPases is an effective technique with broader implications of nanobody development into therapeutics.NAUpstate Medical UniversityBiochemistry & Molecular BiologyPhDWilkens, Stepha

Optimizing variables for contingency management among infant caregivers using a simulated purchase task

Behavioral economics offers a framework for understanding choice making around public health concerns such as drug use and distracted driving. Such a framework could be beneficial to understanding caregiver choices related to arranging an infant sleep environment. Nonadherence to infant sleep safety guidelines provided by the American Academy of Pediatrics increases the risk of sleep-related infant deaths. The present study adopted a willingness-to-accept purchase task procedure, used in previous research to evaluate variables that predict abstaining from consuming alcohol, to evaluate intention to adhere to recommendations for arranging a safe infant sleep environment. This analysis would inform contingency management incentive scales used to measure caregiver adherence following training caregivers to arrange an infant sleep environment and identify variables that might predict treatment engagement. The results identified incentive sizes, condition duration, and participant variables that predict caregiver adherence. The results can be applied to future investigations that train caregivers to arrange an infant sleep environment.AMSUNY DownstateApplied Behavior AnalysisN/

Predicting the Risk of Depression Based on the Patient's Chronic Diseases and Other Physiological Attributes

The prevalence of chronic diseases like diabetes, hypertension, and chronic respiratory conditions contributes significantly to global mortality rates. In addition, there is growing evidence that links mental health disorders to physical activity, body mass index (BMI), and chronic diseases, highlighting their importance in public health research. This study investigates the intricate relationship between chronic diseases and depression, employing innovative Machine Learning techniques to predict depression likelihood based on various health comorbidities. Results indicate that Naive Bayes consistently outperforms other models, highlighting its potential for accurate predictions. The trade-off between specificity and accuracy, however, highlights the necessity of balanced datasets in real-world applications.NASUNY PlattsburghManagement Informations Systems and AnalyticsN/ABushaj, Saba

Optimising early detection of degenerative cervical myelopathy: a systematic review of quantitative screening tools for primary care

Background: Early diagnosis of degenerative cervical myelopathy (DCM) is often challenging due to subtle, non-specific symptoms, limited disease awareness and a lack of definitive diagnostic criteria. As primary care physicians are typically the first to encounter patients with early DCM, equipping them with effective screening tools is crucial for reducing diagnostic delays and improving patient outcomes. This systematic review evaluates the efficacy of quantitative screening methods for DCM that can be implemented in primary care settings. Methods: A systematic search following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted across PubMed, Embase and Cochrane Library up to July 2024 using keywords relevant to DCM screening. Studies were included if they evaluated the sensitivity and specificity of DCM screening tools applicable to primary care settings. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results: The search identified 14 studies evaluating 18 screening methods for DCM. Questionnaires consistently showed high diagnostic accuracy, with Youden indices exceeding 0.60, while only three out of nine conventional physical performance tests met the same threshold. Sensor-assisted tests, particularly those using advanced technology like finger-wearable gyro sensors, exhibited the highest diagnostic accuracy but present challenges related to accessibility and learning curves. Conclusion: This review highlights the potential of quantitative screening methods for early DCM detection in primary care. While questionnaires and conventional tests are effective and accessible, sensor-assisted tests offer greater accuracy but face implementation challenges. A tailored, multifaceted approach is crucial for improving outcomes. Future research should focus on validating these tools in diverse populations and standardising diagnostic criteria.VoRSUNY DownstateMedicineN/

Nanotherapeutics for Immune Modulation in Sepsis

Due to its complexity and heterogeneity, managing immune dysregulation in sepsis poses a significant clinical challenge. Thus, there is great demand to both improve our understanding of mediators of immune dysregulation in sepsis and develop nuanced therapeutic approaches to provide precise immune modulation for sepsis treatment. This thesis first investigates the novel phenomenon of cytokine charge disparity as a potential regulator of cytokine function. Then, two novel telodendrimer immune modulation approaches are presented as a personalized medicine strategy for sepsis. Through extensive database and literature review, we have established cytokine charge disparity as a potential mechanism for immune regulation. Using our versatile telodendrimers (TDs), we then optimized and validated our TD nanotrap approach for effective and selective targeting of plasma cytokines. Our lead selective TD nanotraps displayed charge selective cytokine targeting and our lead pan-affinitive TD nanotrap demonstrated superior cytokine removal efficacy compared to commercial resin control. Additionally, pan-affinitive TD nanotrap maintained efficacy across a wide range patient immune status, indicating promising therapeutic potential to reduce mortality risk associated with overwhelming cytokine profiles. To further expand our immune modulation tool set for sepsis treatment, we optimized our TD nanodrug for delivery of dimethyl itaconate (ITA) to control both hyperinflammation and pyroptosis. Encapsulating ITA into TD nanoparticles (ITA:TDNPs) resulted in a sustained-release profile and improved biocompatibility compared to free ITA. ITA:TDNPs more effectively inhibited both LPS- and LTA-induced inflammation and pyroptosis in macrophages compared to ITA or TDNP alone. Finally, ITA:TDNPs demonstrated superior therapeutic efficacy in both an IV LPS and polymicrobial cecal slurry sepsis model compared to individual therapies. Collectively, we have uncovered a novel phenomenon of cytokine charge disparity and validated it as a potential mechanism to regulate cytokine activity, as well as established it as targeting mechanism for effective immune modulation via charge selective TD nanotrap. We further developed an immune modulating TD nanodrug for ITA delivery to control both hyperinflammation and immune cell pyroptosis in sepsis. Through precise targeting of immune dysregulation in sepsis using a systematic multimodal TD therapeutic approach for personalized medicine, we may successfully improve patient outcomes in this devastating disease.NAUpstate Medical UniversityPharmacologyPhDLuo, Junta

Engineering Generalized Protein-Based Biosensors for Molecular Detection and Clinical Applications

Protein-based conformational switches serve as powerful tools for the construction of biosensors and for the control of cellular processes. These proteins feature a binding domain that recognizes a specific analyte and is coupled to an output domain in such a way that the binding event causes the output domain to provide an observable signal. These signals can either be turn-on of fluorescence, luminescence, or enzymatic activity or consist of the sensor changing its color. A challenge in constructing these protein switches is finding binding domains capable of relaying a ligand binding event to the conformational change of an output domain. Generalized binding domains can address these challenges by providing a scaffold that can easily be modified to detect a different ligand. These generalized binding domains are small proteins with modifiable residues that can be selected to bind a ligand of choice, usually through phage display and similar selection techniques. Here, we present two approaches to make generalized protein switches. In the first approach, antibody mimetics nanobodies and monobodies are inserted in fluorescent proteins such that binding of their ligand causes an increase in fluorescence. This technique, named adaptable turn-on maturation (ATOM), was used to develop biosensors for WD-40 repeat protein 5 (WDR5), c-Abl src homology 2 (SH2) domain, hRas, postsynaptic density protein 95 (PSD95), gephyrin, HOMER1, and mCherry for use in mammalian cells. ATOM is, therefore, compatible with a variety of ligands due to its input domain being a generalized binding domain. Additionally, the ATOM mechanism can be used to convert many fluorescent proteins into biosensors. For demonstration, we made biosensors from Clover, mTurqoise, mTagRFP-t, mStayGold, mBaoJin, and GCaMP6s. In the second approach, we develop a luminescent protein switch from the enzyme nanoluciferase (nLucAFF) that switches color from green to blue upon DNA binding. We show that DNA-based devices can then be used to detect various ligands and relay that event to nLucAFF, which provides an output easily quantifiable by a cell phone. The nLucAFF protein was used to detect DNA sequences amplified from cytomegalovirus (CMV), dengue, and nCoV. Additionally, aptamers binding to serotonin and aptamers were used to detect these molecules by directing the nLucAFF color change. The initial version of nLucAFF was slow, dim, and had low sensitivity. These drawbacks were resolved in the next version, nLucAFF2, to achieve turn-on within 5 minutes and detect ligands down to 40 pM with a cell phone camera. The last chapter combines two ligand-binding domains to activate a small cytotoxic RNase, barnase, and paves the way for the development of multi-input protein switches that can potentially be generalized ligand-binding domains.NAUpstate Medical UniversityBiochemistry & Molecular BiologyPhDLoh, Stewar

Association between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosis

Purpose: The aim of this study was to investigate the relationship between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosis (ALS). Methods: The heart activity of 65 patients with ALS (28 with normal cognition [ALS-CN]; 37 with impaired cognition [ALS-CI]) and 38 healthy controls (HCs) was measured by 24-h Holter monitoring. Heart rate (HR) measures and heart rate variability (HRV) parameters were compared between the three study groups and, additionally, correlated with five Edinburgh Cognitive and Behavioral ALS Screen (ECAS) domains in the ALS subgroups. Age, gender, and educational level were adjusted. Factors associated with cognitive status were assessed using logistic regression. Survival predictors in patients with ALS were analyzed using the Kaplan-Meier estimator and Cox regression. Results: Compared to the HCs, patients with ALS-CI exhibited lower RRI (R-R-interval; P = 0.017), SDNN (standard deviation of all normal RR intervals; P = 0.013), SDNN Index (P = 0.044), and VLF power (very low-frequency power; P = 0.012). Total power was reduced in the ALS-CI group compared to the HCs (P = 0.036) and ALS-CN group (P = 0.048). In patients with ALS-CN, language negatively correlated with mean HR (P = 0.001) and positively with the RRI (P = 0.003), SDNN (P = 0.001), SDANN (standard deviation of the average NN intervals; P = 0.005), total power (P = 0.006), VLF power (P = 0.011), and low-frequency power (P = 0.026). Visuospatial function correlated positively with the SDNN Index (P = 0.041). In patients with ALS-CI, executive function (P = 0.015) and ECAS total score (P = 0.009) negatively correlated with the RMSSD (square root of mean sum-of-squares of differences between adjacent NN intervals), while visuospatial function correlated positively with normalized LF value (LFnu; P = 0.049). No associations were observed between the other cognitive domains and any of the 14 HRV/HR measures in patients with either ALS-CI or ALS-CN. SDNN ≤ 100 ms was linked to cognitive impairment (P = 0.039) and also showed a borderline association (P = 0.066) with poorer survival, while cognitive impairment (P = 0.010) was significantly linked to worse outcomes. Conclusions: Patients with ALS with cognitive impairment demonstrated reduced cardiac autonomic modulations and altered cognitive autonomic associations. Cognitive impairment was linked to reduced survival, with baseline SDNN ≤ 100 ms identified as a potential marker.the National Natural Science Foundation of ChinaVoRSUNY DownstateNeurologyN/

Hopis and the Counterculture Traditionalism, Appropriation, and the Birth of a Social Field

Dr. Brian Haley from the Department of Anthropology present his recently published book Hopis and the Counterculture: Traditionalism, Appropriation, and the Birth of a Social Field.This book addresses how the Hopi became icons of the followers of alternative spiritualities and reveals one of the major pathways for the explosive appropriation of Indigenous identities in the 1960s. It reveals a largely unknown network of Native, non-Indian, and neo-Indian actors who spread misrepresentations of the Hopi that they created through interactions with the Hopi Traditionalist faction of the 1940s through 1980s. Significantly, many non-Hopis involved adopted Indian identities during this time, becoming "neo-Indians." Exploring the new social field that developed to spread these ideas, Hopis and the Counterculture meticulously traces the trajectories of figures such as Ammon Hennacy, Craig Carpenter, Frank Waters, and the Firesign Theatre, among others.VoRSUNY OneontaAnthropologyN/