The Global Pandemic is Still Global

Californians feel an understandable sense of relief as the economy is reopened and more normal life resumes. But COVID‐19 is still killing hundreds if not thousands of people around the country, and many, many more in countries where vaccine supplies are far less available or not at all. Less than 10 percent of the world’s population has been fully vaccinated, most of them in rich industrialized nations like ours. In other countries like Mexico, where I grew up and still have a large family, only about 12 percent of the population of about 130 million has been fully vaccinated and the total number of deaths is estimated at around 600,000. These numbers are abstractions until they touch you personally. Through all of 2020 no one in my family got sick with COVID‐19, but that changed quickly this year: first my mother got it, then one of my sisters, then two of my brothers along with members of their families. My younger brother, Paco, died after three weeks in intensive care, while Luis miraculously survived after being unconscious in the ICU for almost two months. Paco’s death has shaken our family on both sides of the border in unimaginable ways, and I feel deep sorrow and empathy for the millions here with relatives all around the world suffering terrible losses who can’t practice the rituals for the dead because of the pandemic. It is easy to focus on our immediate surroundings and ignore the great pain and suffering that many parts of our one world are still experiencing. This is a worldwide pandemic and no one is completely safe until everyone is safe from this terrible disease. Solidarity with our local neighbors who lost relatives and friends in distant places is a good way for me to remember my brother Paco and for all of us to honor our common humanity

Experiencing Poverty in an Online Simulation: Effects on Players’ Beliefs, Attitudes and Behaviors about Poverty

Digital simulations are increasingly used to educate about the causes and effects of poverty, and inspire action to alleviate it. Drawing on research about attributions of poverty, subjective well-being, and relative income, this experimental study assesses the effects of an online poverty simulation (entitled Spent) on participants’ beliefs, attitudes, and actions. Results show that, compared with a control group, Spent players donated marginally more money to a charity serving the poor and expressed higher support for policies benefitting the poor, but were less likely to take immediate political action by signing an online petition to support a higher minimum wage. Spent players also expressed greater subjective well-being than the control group, but this was not associated with increased policy support or donations. Spent players who experienced greater presence (perceived realism of the simulation) had higher levels of empathy, which contributed to attributing poverty to structural causes and support for anti-poverty policies. We draw conclusions for theory about the psychological experience of playing online poverty simulations, and for how they could be designed to stimulate charity and support for anti-poverty policies

Designing the Online Collaboratory for the Global Social Benefit Incubator

Pedro Hernandez-Ramos, James L. Koch, Albert Bruno, and Eric Carlson describe the online collaboratory planned for the Global Social Benefit Incubator (GSBI), an international education program designed to serve social benefit entrepreneurs working in the fields of education, health, economic development, the environment, and equality around the world, primarily in developing countries. Hosted by Santa Clara University, the GSBI has held two-week intensive workshops for selected social benefit entrepreneurs since 2003. The program has identified two major goals for its development: (1) establishing an innovative, blended learning environment (face-to-face and online) capable of addressing the needs of a wide range of learners and (2) extending the program\u27s reach via an online communication, collaboration, and learning environment. Current technological resources are inadequate to the program\u27s long-term goals, leading to the need to develop an extended collaboratory where participants could continue to contribute long after the end of their residential experience. Key objectives for this developmental research project include the design or adaptation of online tools that support distributed knowledge construction, skill development, communication, and collaboration for learners with different backgrounds, capabilities, language skills, interests, and priorities. The authors posit that project outcomes would be meaningful at two complementary levels: pedagogical innovations addressing heterogeneous adult learner populations and innovations in the design of online learning environments

Postoperative Pain in Pediatrics

Postoperative pain in pediatrics is a common concern for both parents and healthcare professionals. Children who experience pain after surgery can present with several complications, including nausea, vomiting, breathing difficulties, sleep disturbances, and decreased physical activity. In addition, untreated pain can have long-term effects on children’s emotional and psychological well-being. It is important to recognize that children may experience pain differently than adults and, therefore, need a personalized treatment approach. Evaluation and management of postoperative pain in pediatrics should be based on the child’s age, the type of surgery, and the severity of pain. Several treatment options are available, including oral, intravenous, and epidural analgesics, as well as non-pharmacological techniques such as relaxation and distraction. Prevention of postoperative pain is also important and can be achieved through the administration of analgesics prior to surgery and early postoperative care

The timing of the deglaciation in the Atlantic Iberian mountains:Insights from the stratigraphic analysis of a lake sequence in Serra da Estrela (Portugal)

Understanding the environmental response to the last glacial termination in regions located in transitional climate zones such as the Atlantic Iberian mountains is crucial to estimate potential changes in regions affected by current glacial melting. We present an 8.5 m-long, solid last deglaciation and Holocene chronostratigraphic record including detailed sediment analysis from Lake Peixão, a pro-glacial lake in the Serra da Estrela (Central Portugal). The age–depth model relies on a Bayesian approach that includes 16 AMS 14C dates and 210Pb–137CS measurements, robustly dating the lake formation at 14.7 ± 0.32 cal. ka BP. This chronological reconstruction shows an average sedimentation rate of ca. 0.07 cm yr−1 (15 yr cm−1), enabling proxy analyses at decadal timescales. The sediment sequence is composed of five lithological units: (U1) coarse and unsorted fluvioglacial lacustrine deposits; (U2) massive fluvioglacial lacustrine deposits (863–790 cm below surface [bsf]; 14.7 ± 0.32–13.8 ± 0.12 cal. ka BP); (U3) water current fluvioglacial lacustrine deposits (790–766 cm bsf; 13.8 ± 0.12–12.9 ± 0.29 cal. ka BP); (U4) laminated/banded lacustrine deposits characterized by terrigenous deposits from ice-covered lake periods and episodic events of ice and snow melting (766–752 cm bsf; 12.9 ± 0.29–11.7 ± 0.15 cal. ka BP); and (U5) massive muddy lacustrine deposits (752–0 cm bsf; 11.7 ± 0.15 cal. ka BP–present). The occurrence of U2 to U4 deposits defines the transition from glacial cold (U1) to net warm postglacial conditions (U5). These climate transitions are marked by changes in sediments and the presence of very low sedimentation rate periods, possibly related to the Intra-Allerød Cold Period and the coldest phase of the Younger Dryas. Our results support the previously proposed timing of the retreat of the Serra da Estrela glaciers ca. 13.8 ± 0.12 cal. ka BP. The robust chronology of Lake Peixão highlights the potential of Iberian pro-glacial lakes for dating deglaciation processes and will lead to unprecedented decadal-to-centennial timescale palaeoclimate reconstructions in this region since the last glacial–interglacial transition

Lentiviral gene therapy reverts GPIX expression and phenotype in Bernard-Soulier syndrome type C

Bernard-Soulier syndrome (BSS) is a rare congenital disease characterized by macrothrombocytopenia and frequent bleeding. It is caused by pathogenic variants in three genes (GP1BA, GP1BB, or GP9) that encode for the GPIbα, GPIbβ, and GPIX subunits of the GPIb-V-IX complex, the main platelet surface receptor for von Willebrand factor, being essential for platelet adhesion and aggregation. According to the affected gene, we distinguish BSS type A1 (GP1BA), type B (GP1BB), or type C (GP9). Pathogenic variants in these genes cause absent, incomplete, or dysfunctional GPIb-V-IX receptor and, consequently, a hemorrhagic phenotype. Using gene-editing tools, we generated knockout (KO) human cellular models that helped us to better understand GPIb-V-IX complex assembly. Furthermore, we developed novel lentiviral vectors capable of correcting GPIX expression, localization, and functionality in human GP9-KO megakaryoblastic cell lines. Generated GP9-KO induced pluripotent stem cells produced platelets that recapitulated the BSS phenotype: absence of GPIX on the membrane surface and large size. Importantly, gene therapy tools reverted both characteristics. Finally, hematopoietic stem cells from two unrelated BSS type C patients were transduced with the gene therapy vectors and differentiated to produce GPIX-expressing megakaryocytes and platelets with a reduced size. These results demonstrate the potential of lentiviral-based gene therapy to rescue BSS type C

Introductions of West Nile Virus Strains to Mexico

Complete genome sequencing of 22 West Nile virus isolates suggested 2 independent introductions into Mexico. A previously identified mouse-attenuated glycosylation variant was introduced into southern Mexico through the southeastern United States, while a common US genotype appears to have been introduced incrementally into northern Mexico through the southwestern United States

Clinical, biological, and prognostic implications of SF3B1 co-occurrence mutations in very low/low- and intermediate-risk MDS patients

SF3B1 is a highly mutated gene in myelodysplastic syndrome (MDS) patients, related to a specific subtype and parameters of good prognosis in MDS without excess blasts. More than 40% of MDS patients carry at least two myeloid-related gene mutations but little is known about the impact of concurrent mutations on the outcome of MDS patients. In applying next-generation sequencing (NGS) with a 117 myeloid gene custom panel, we analyzed the co-occurrence of SF3B1 with other mutations to reveal their clinical, biological, and prognostic implications in very low/low- and intermediate-risk MDS patients. Mutations in addition to those of SF3B1 were present in 80.4% of patients (median of 2 additional mutations/patient, range 0–5). The most frequently mutated genes were as follows: TET2 (39.2%), DNMT3A (25.5%), SRSF2 (10.8%), CDH23 (5.9%), and ASXL1, CUX1, and KMT2D (4.9% each). The presence of at least two mutations concomitant with that of SF3B1 had an adverse impact on survival compared with those with the SF3B1 mutation and fewer than two additional mutations (median of 54 vs. 87 months, respectively: p = 0.007). The co-occurrence of SF3B1 mutations with specific genes is also linked to a dismal prognosis: SRSF2 mutations were associated with shorter overall survival (OS) than SRSF2wt (median, 27 vs. 75 months, respectively; p = 0.001), concomitant IDH2 mutations (median OS, 11 [mut] vs. 75 [wt] months; p = 0.001), BCOR mutations (median OS, 11 [mut] vs. 71 [wt] months; p = 0.036), and NUP98 and STAG2 mutations (median OS, 27 and 11 vs. 71 months, respectively; p = 0.008 and p = 0.002). Mutations in CHIP genes (TET2, DNMT3A) did not significantly affect the clinical features or outcome. Our results suggest that a more comprehensive NGS study in low-risk MDS SF3B1mut patients is essential for a better prognostic evaluation.This work was supported by grants from the following: Contrato Rio Hortega, CM17/00171; Gerencia Regional de Salud (Castilla y León) para proyectos de investigación año 2018, 1850/A/18; Spanish Fondo de Investigaciones Sanitarias, PI15/01471, PI18/01500; Instituto de Salud Carlos III (ISCIII); European Regional Development Fund (ERDF) “Una manera de hacer Europa”; Consejería de Educación, Junta de Castilla y León (SA271P18); Proyectos de Investigación del SACYL, Spain, GRS1847/A/18, GRS1653/A17; SYNtherapy, Synthetic Lethality for Personalized Therapy-based Stratification In Acute Leukemia (ERAPERMED2018–275); ISCIII (AC18/00093), co-funded by ERDF/ESF, “Investing in your future”, by grants from Red Temática de Investigación Cooperativa en Cáncer (RTICC) (RD12/0036/0069) and Centro de Investigación Biomédica en Red de Cáncer (CIBERONC CB16/12/00233). JMHS is supported by a research grant from Fundación Española de Hematología y Hemoterapia. MM is currently supported by an Ayuda predoctoral de la Junta de Castilla y León from the Fondo Social Europeo (JCYL- EDU/556/2019 PhD scholarship)