G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer

Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ERα), progesterone receptor (PR), and HER2 (ErbB2) and exhibit increased glutamine metabolism, a requirement for tumor growth. The G protein-coupled kisspeptin receptor (KISS1R) is highly expressed in patient TNBC tumors and promotes malignant transformation of breast epithelial cells. This study found that TNBC patients displayed elevated plasma kisspeptin levels compared with healthy subjects. It also provides the first evidence that in addition to promoting tumor growth and metastasis in vivo, KISS1R-induced glutamine dependence of tumors. In addition, tracer-based metabolomics analyses revealed that KISS1R promoted glutaminolysis and nucleotide biosynthesis by increasing c-Myc and glutaminase levels, key regulators of glutamine metabolism. Overall, this study establishes KISS1R as a novel regulator of TNBC metabolism and metastasis, suggesting that targeting KISS1R could have therapeutic potential in the treatment of TNBC

OPEnS Hub: Real-time Data Logging, Connecting Field Sensors to Google Sheets

In Earth science, we must often collect data from sensors installed in remote locations. Retrieving these data and storing them can be challenging. Present options include proprietary commercial dataloggers, communication devices, and protocols with rigid software and data structures that may require ongoing expenses. While there are open-source solutions that include telemetry, such as EnviroDIY’s Mayfly, none presently generate real-time, remotely accessible workbooks (EnviroDIY, 2018). The Openly Published Environmental Sensing (OPEnS) Lab developed the OPEnS Hub, a new approach to using low-power, open-source hardware and software to achieve real-time data logging from the field to the web. The Hub is an order of magnitude less expensive than commercial products, inherently modular and flexible, and aims to reduce technical barriers for users with little programming experience (DeBell, 2019). Data can be collected remotely using a host of transmission protocols to relay data from distributed in-situ monitoring devices. The Hub mesh-networks with several nodes and backs up to an onboard microSD card. Telemetry options include 900 MHz Long Range Radio (LoRa) with up to 25 km range and Nordic Radio Frequency (nRF) for higher data rates (Adafruit Industry, 2019). Ongoing transmissions from the Hub to the internet currently employ Ethernet with potential support for Wi-Fi and the cell network. The Hub engages a dynamic, low latency portal to Google Sheets via the free Application Programming Interface (API), PushingBox, and an adaptable Google Apps Script. This framework was tested on 12 individual sensors nodes at remote sites in Oregon. This manuscript details our methods and evaluates PushingBox, Google Apps Script, Adafruit Industries’ open-hardware Feather development boards, the Hypertext Transfer Protocol (HTTP), and the aforementioned modes of data transfer

The epidemiology of injuries across the weight-training sports

Background: Weight-training sports, including weightlifting, powerlifting, bodybuilding, strongman, Highland Games, and CrossFit, are weight-training sports that have separate divisions for males and females of a variety of ages, competitive standards, and bodyweight classes. These sports may be considered dangerous because of the heavy loads commonly used in training and competition. Objectives: Our objective was to systematically review the injury epidemiology of these weight-training sports, and, where possible, gain some insight into whether this may be affected by age, sex, competitive standard, and bodyweight class. Methods: We performed an electronic search using PubMed, SPORTDiscus, CINAHL, and Embase for injury epidemiology studies involving competitive athletes in these weight-training sports. Eligible studies included peer-reviewed journal articles only, with no limit placed on date or language of publication. We assessed the risk of bias in all studies using an adaption of the musculoskeletal injury review method. Results: Only five of the 20 eligible studies had a risk of bias score ≥75 %, meaning the risk of bias in these five studies was considered low. While 14 of the studies had sample sizes >100 participants, only four studies utilized a prospective design. Bodybuilding had the lowest injury rates (0.12–0.7 injuries per lifter per year; 0.24–1 injury per 1000 h), with strongman (4.5–6.1 injuries per 1000 h) and Highland Games (7.5 injuries per 1000 h) reporting the highest rates. The shoulder, lower back, knee, elbow, and wrist/hand were generally the most commonly injured anatomical locations; strains, tendinitis, and sprains were the most common injury type. Very few significant differences in any of the injury outcomes were observed as a function of age, sex, competitive standard, or bodyweight class. Conclusion: While the majority of the research we reviewed utilized retrospective designs, the weight-training sports appear to have relatively low rates of injury compared with common team sports. Future weight-training sport injury epidemiology research needs to be improved, particularly in terms of the use of prospective designs, diagnosis of injury, and changes in risk exposure

Supervising the Supervisors—Procedural Training and Supervision in Internal Medicine Residency

At teaching hospitals, bedside procedures (paracentesis, thoracentesis, lumbar puncture, arthrocentesis and central venous catheter insertion) are performed by junior residents and supervised by senior peers. Residents’ perceptions about supervision or how often peer supervision produces unsafe clinical situations are unknown. To examine the experience and practice patterns of residents performing bedside procedures. Cross-sectional e-mail survey of 653 internal medicine (IM) residents at seven California teaching hospitals. Surveys asked questions in three areas: (1) resident experience performing procedures: numbers of procedures performed and whether they received other (e.g., simulator) training; (2) resident comfort performing and supervising procedures; (3) resident reports of their current level of supervision doing procedures, experience with complications as well as perceptions of factors that may have contributed to complications. Three hundred sixty-seven (56%) of the residents responded. Most PGY1 residents had performed fewer than five of any of the procedures, but most PGY-3 residents had performed at least ten by the end of their training. Resident comfort for each procedure increased with the number of procedures performed (p < 0.001). Although residents reported that peer supervision happened often, they also reported high rates of supervising a procedure before feeling comfortable with proper technique. The majority of residents (64%) reported at least one complication and did not feel supervision would have prevented complications, even though many reported complications represented technique- or preparation-related problems. Residents report low levels of comfort and experience with procedures, and frequently report supervising prior to feeling comfortable. Our findings suggest a need to examine best practices for procedural supervision of trainees

Digitization workflows for flat sheets and packets of plants, algae, and fungi

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141708/1/aps31500065.pd

Strategies to overcome physician shortages in northern Ontario: A study of policy implementation over 35 years

<p>Abstract</p> <p>Background</p> <p>Shortages and maldistibution of physicians in northern Ontario, Canada, have been a long-standing issue. This study seeks to document, in a chronological manner, the introduction of programmes intended to help solve the problem by the provincial government over a 35-year period and to examine several aspects of policy implementation, using these programmes as a case study.</p> <p>Methods</p> <p>A programme analysis approach was adopted to examine each of a broad range of programmes to determine its year of introduction, strategic category, complexity, time frame, and expected outcome. A chronology of programme initiation was constructed, on the basis of which an analysis was done to examine changes in strategies used by the provincial government from 1969 to 2004.</p> <p>Results</p> <p>Many programmes were introduced during the study period, which could be grouped into nine strategic categories. The range of policy instruments used became broader in later years. But conspicuous by their absence were programmes of a directive nature. Programmes introduced in more recent years tended to be more complex and were more likely to have a longer time perspective and pay more attention to physician retention. The study also discusses the choice of policy instruments and use of multiple strategies.</p> <p>Conclusion</p> <p>The findings suggest that an examination of a policy is incomplete if implementation has not been taken into consideration. The study has revealed a process of trial-and-error experimentation and an accumulation of past experience. The study sheds light on the intricate relationships between policy, policy implementation and use of policy instruments and programmes.</p

Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with 99mTc- and 123I-labelled probes

The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of (123)I- and (99m)Tc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake.A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D(2) receptor ligand [(123)I]IBZM and the cerebral perfusion tracer [(99m)Tc]HMPAO (1.2-0.4 MBq/g body weight) in healthy mice. The fatty acid [(123)I]IPPA (0.94 +/- 0.05 MBq/g body weight) and the perfusion tracer [(99m)Tc]sestamibi (3.8 +/- 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP(3) receptor.In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [(123)I]IBZM and of cardiac [(99m)Tc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [(123)I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [(99m)Tc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [(123)I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight.Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of (123)I- and (99m)Tc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers

Timing and Tempo of Early and Successive Adaptive Radiations in Macaronesia

The flora of Macaronesia, which encompasses five Atlantic archipelagos (Azores, Canaries, Madeira, Cape Verde, and Salvage), is exceptionally rich and diverse