Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer.

BACKGROUND: Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician's choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair-proficient (pMMR) disease and in all patients. Safety was also assessed. RESULTS: A total of 827 patients (697 with pMMR disease and 130 with mismatch repair-deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy. CONCLUSIONS: Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer. (Funded by Eisai and Merck Sharp and Dohme [a subsidiary of Merck]; Study 309-KEYNOTE-775 ClinicalTrials.gov number, NCT03517449.).

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma.

BACKGROUND: Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear. METHODS: In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated. RESULTS: A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P = 0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P = 0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels. CONCLUSIONS: Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).

Sympatry and parapatry among rocky reef cichlids of Lake Victoria explained by female mating preferences.

Work on the Lake Victoria cichlids Pundamilia nyererei (red dorsum males, deeper water), Pundamilia pundamilia (blue males, shallower water) and related species pairs has provided insights into processes of speciation. Here, we investigate the female mating behaviour of 5 Pundamilia species and 4 of their F1 hybrids through mate choice trials and paternity testing. Complete assortative mating was observed among all sympatric species. Parapatric species with similar depth habitat distributions interbred whereas other parapatric and allopatric species showed complete assortative mating. F1 hybrids mated exclusively with species accepted by females of the parental species. The existence of complete assortative mating among some currently allopatric species suggests that pre-existing mating barriers could be sufficient to explain current patterns of co-existence, although, of course, many other factors may be involved. Regardless of the mechanism, mating preferences may influence species distribution in potentially hybridizing taxa, such as in the adaptive radiation of cichlid fish. We suggest that this at least partly explains why some species fail to establish breeding populations in locations where they are occasionally recorded. Our results support the notion that the mating preferences of potentially cross-breeding species ought to be included in coexistence theory.

The Scalding Truth: Geospatial Analysis Identifies Communities at Risk for Pediatric Scald Burns.

INTRODUCTION: Pediatric scald burns account for 12% of all U.S. burn center admissions and are the most common type of burn in children. We hypothesized that geospatial analysis of burn registry data could identify specific geographic areas and risk factors to focus injury prevention efforts. METHODS: The burn registry of a U.S. regional burn center was used to retrospectively identify pediatric scald burn patients ages 0-17, from January 2018 to June 2023. Geocoding of patient home addresses with census tract data was performed. Area Deprivation Index (ADI) was assigned to patients at the census block group level. Burn incident hot spot analysis to identify statistically significant burn incident clusters was done using the Getis Ord Gi∗ statistic. RESULTS: There were 950 pediatric scald burn patients meeting study criteria. The cohort was 52% male and 36% White, with median age of 3 y and median total body surface area of 1.5%; 23.8% required hospital admission. On multivariable logistic regression, increased child poverty levels (P = 0.004) and children living in single-parent households (P = 0.009) were associated with increased scald burn incidence. Geospatial analysis identified burn hot spots, which were associated with higher ADI (P < 0.001). Black patients were more likely to undergo admission compared to White patients. CONCLUSIONS: Geospatial analysis of burn registry data identified geographic areas at high risk of pediatric scald burn. ADI, poverty, and children in single-parent households were the greatest predictors of injury. Addressing these inequalities requires targeted injury prevention education, enhanced outpatient support systems and more robust community resources.

Identification and management of low-risk isolated traumatic brain injury patients initially treated at a rural level IV trauma center.

STUDY OBJECTIVE: Our goal was to determine if low-risk, isolated mild traumatic brain injury (TBI) patients who were initially treated at a rural emergency department may have been safely managed without transfer to the tertiary referral trauma center. METHODS: This was a retrospective observational analysis of isolated mild TBI patients who were transferred from a rural Level IV Trauma Center to a regional Level I Trauma Center between 2018 and 2022. Patients were risk-stratified according to the modified Brain Injury Guidelines (mBIG). Data abstracted from the electronic medical record included patient presentation, management, and outcomes. RESULTS: 250 patients with isolated mild TBI were transferred out to the Level I Trauma Center. Fall was the most common mechanism of injury (69.2%). 28 patients (11.2%) were categorized as low-risk (mBIG1). No mBIG1 patients suffered a progression of neurological injury, had worsening of intracranial hemorrhage on repeat head CT, or required neurosurgical intervention. 12/28 (42.9%) of mBIG1 patients had a hospital length of stay of 2 days or less, typically for observation. Those with longer lengths of stay were due to medical complications, such as sepsis, or difficulty in arranging disposition. CONCLUSION: We propose that patients who meet mBIG1 criteria may be safely observed without transfer to a referral Level I Trauma Center. This would be of considerable benefit to patients, who would not need to leave their community, and would improve resource utilization in the region.

Physical Activity Behaviors of Female Adolescents in Saudi Arabia.

BACKGROUND: Saudi Arabia has one of the highest childhood obesity rates worldwide. The primary factor associated with the high prevalence of obesity among adolescents is a lack of physical activity (PA). Compared to male adolescents, very few Saudi female adolescents meet the World Health Organization recommendation of achieving 60 minutes of moderate-to-vigorous PA per day, putting them at a higher risk of overweight and obesity. OBJECTIVE: This cross-sectional study aimed to examine the relationship between the theory of planned behavior and psychosocial factors, including attitude toward PA, subjective norms, perceived behavioral control (PBC), PA intention, and self-reported PA among Saudi female adolescents. METHODS: A convenience sample of 329 Saudi female adolescents was recruited from all-female public intermediate and high schools in the Eastern Region of Saudi Arabia. Data were collected using online self-administered questionnaires. The theoretical model was examined using structural equation modeling. RESULTS: The findings revealed a higher prevalence of overweight compared to obesity among participants. About half the participants were from families with a medium monthly income. The mean PA score indicated a low level of PA. The model demonstrated significant explanatory power for both PA intention and PA behavior, respectively. The strongest predictor of adolescents' intention was attitude, followed by PBC.Moreover, the female adolescents' attitudes and PBC had significant indirect effects on self-reported PA through intention, whereas intention had a direct effect on PA. The model did not support a direct or indirect relationship between subjective norms and PA. DISCUSSION: The findings provide essential support for targeting attitude and perceived behavior control of female adolescents in order to enhance their PA intention. This theoretical understanding can help design effective theory-based interventions that promote PA among Saudi female adolescents.

Morality- and Norm-Based Subgroups of Disability-Sport Athletes Differ on Their Anticipated Guilt and Intentions Toward Doping.

The purpose of this study was to examine whether subgroups of disability-sport athletes exist on morality- and norm-based doping cognitions and whether these groups differ in anticipated guilt or doping intentions. A survey was completed by 186 athletes (Mage = 37.5 years, 78.0% male, 45.1% wheelchair basketball) assessing norms, doping moral disengagement, anticipated guilt, and intentions to dope. Cluster analysis revealed four distinct subgroups of athletes, including one potentially high-risk subgroup characterized by relatively high scores on doping moral disengagement, subjective norms, and descriptive norms. One-way analysis of variance revealed significantly lower anticipated guilt in two athlete subgroups characterized by relatively higher doping moral disengagement than the other two subgroups. Moreover, the potentially high-risk group had a greater proportion of athletes showing some presence of intention to dope. This study suggests there is a small subgroup of disability-sport athletes at elevated risk of doping who might benefit from targeted antidoping interventions.

Perspectives of Rural High School Students Involved in a Multi-Component, After-School Physical Activity Intervention.

After-school physical activity interventions can assist high school students in meeting physical activity recommendations; however, little is known about what kinds of programs work best for students in rural settings. The purpose of this qualitative study was to explore rural high school students' perceptions of a multi-component, after-school physical activity intervention. Interviews were conducted with 10 students who had participated in a physical activity intervention. Thematic analysis was conducted on the interviews. Participants indicated that the intervention provided a supportive and motivating environment through the use of innovative technology and peer relatedness/involvement. Although barriers such as time constraints often prevented them from achieving their weekly goals, students expressed overall satisfaction with the intervention and a heightened self-motivation for physical activity. The qualitative approach provides a greater understanding of the perspectives of rural adolescents participating in a physical activity intervention. Findings can be useful to school nurses and inform the development of future physical activity interventions.

Small bowel obstruction in older patients: challenges in surgical management.

BACKGROUND: Small bowel obstruction (SBO) is a common disease affecting all segments of the population, including the frail elderly. Recent retrospective data suggest that earlier operative intervention may decrease morbidity. However, management decisions are influenced by surgical outcomes. Our goal was to determine the current surgical management of SBO in older patients with particular attention to frailty and the timing of surgery. STUDY DESIGN: A retrospective review of patients over the age of 65 with a diagnosis of bowel obstruction (ICD-10 K56*) using the 2016 National Inpatient Sample (NIS). Demographics included age, race, insurance status, medical comorbidities, and median household income by zip code. Elixhauser comorbidities were used to derive a previously published frailty score using the NIS dataset. Outcomes included time to operation, mortality, discharge disposition, and hospital length of stay. Associations between demographics, frailty, timing of surgery, and outcomes were determined. RESULTS: 264,670 patients were included. Nine percent of the cohort was frail; overall mortality was 5.7%. Frail had 1.82 increased odds of mortality (95% CI 1.64-2.03). Hospital LOS was 1.6 times as long for frail patients; a quarter of the frail were discharged home. Frail patients waited longer for surgery (3.58 days vs 2.44 days; p < 0.001). Patients transferred from another facility had increased mortality (aOR 1.58; 95% CI 1.36-1.83). There was an increasing mortality associated with a delay in surgery. CONCLUSION: Patients with frailty and SBO have higher mortality, more frequent discharge to dependent living, longer hospital length of stay, and longer wait to operative intervention. Mortality is also associated with male gender, black race, transfer status from another facility, self-pay status, and low household income. Every day in delay in surgical intervention for those who underwent operations led to higher mortality. If meeting operative indications, older patients with bowel obstruction have a higher chance of survival if they undergo surgery earlier.

Effect of telepractice on pediatric cochlear implant users and provider vowel space: A preliminary report.

Clear speaking styles are goal-oriented modifications in which talkers adapt acoustic-phonetic characteristics of speech to compensate for communication challenges. Do children with hearing loss and a clinical provider modify speech characteristics during telepractice to adjust for remote communication? The study examined the effect of telepractice (tele-) on vowel production in seven (mean age 4:11 years, SD 1:2 years) children with cochlear implants (CIs) and a provider. The first (F1) and second (F2) formant frequencies of /i/, /ɑ/, and /u/ vowels were measured in child and provider speech during one in-person and one tele-speech-language intervention, order counterbalanced. Child and provider vowel space areas (VSA) were calculated. The results demonstrated an increase in F2 formant frequency for /i/ vowel in child and provider speech and an increase in F1 formant frequency for /ɑ/ vowel in the provider speech during tele- compared to in-person intervention. An expansion of VSA was found in child and provider speech in tele- compared to in-person intervention. In children, the earlier age of CI activation was associated with larger VSA in both tele- and in-person intervention. The results suggest that the children and the provider adjust vowel articulation in response to remote communication during telepractice.

A Systematic Review of eHealth Interventions to Promote Physical Activity in Adults with Obesity or Overweight.

Use of information and communication technology to improve health, known as eHealth, is an emerging concept in healthcare that may present opportunities to promote physical activity in adults with obesity. The purpose of this research was to systematically review eHealth intervention studies to promote physical activity in adults with obesity. Five electronic databases were used. Two authors screened articles, assessed risk of bias, and extracted data independently. A qualitative data synthesis for summarizing the findings was performed using harvest plots. In the search, 2276 articles were identified, and 18 studies met all inclusion criteria. Study quality ranged from poor to good. The included studies varied in intervention technology (e.g., web-based), physical activity assessment (e.g., device-based), and control group (e.g., wait-list). Behavioral change techniques used in the included studies were consistent with some techniques (e.g., self-monitoring) known as effective in face-to-face interventions, but more efficiently employed in eHealth using information and communication technology. Overall, this systematic review showed that a web-based or physical activity monitor-based eHealth intervention had the potential to effectively promote physical activity in adults with obesity. Some recommendations for future eHealth interventions to promote physical activity in adults with obesity were provided (e.g., use of theory, accelerometers).

Ketone Monoester Ingestion Alters Metabolism and Simulated Rugby Performance in Professional Players.

Ketone ingestion can alter metabolism but effects on exercise performance are unclear, particularly with regard to the impact on intermittent-intensity exercise and team-sport performance. Nine professional male rugby union players each completed two trials in a double-blind, randomized, crossover design. Participants ingested either 90 ± 9 g carbohydrate (CHO; 9% solution) or an energy matched solution containing 20 ± 2 g CHO (3% solution) and 590 mg/kg body mass ß-hydroxybutyrate monoester (CHO + BHB-ME) before and during a simulated rugby union-specific match-play protocol, including repeated high-intensity, sprint and power-based performance tests. Mean time to complete the sustained high-intensity performance tests was reduced by 0.33 ± 0.41 s (2.1%) with CHO + BHB-ME (15.53 ± 0.52 s) compared with CHO (15.86 ± 0.80 s) placebo (p = .04). Mean time to complete the sprint and power-based performance tests were not different between trials. CHO + BHB-ME resulted in blood BHB concentrations that remained >2 mmol/L during exercise (p < .001). Serum lactate and glycerol concentrations were lower after CHO + BHB-ME than CHO (p < .05). Coingestion of a BHB-ME with CHO can alter fuel metabolism (attenuate circulating lactate and glycerol concentrations) and may improve high-intensity running performance during a simulated rugby match-play protocol, without improving shorter duration sprint and power-based efforts.

Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study.

BACKGROUND: Despite advances in the first-line treatment of metastatic renal cell carcinoma (RCC), there is an unmet need for options to address disease progression during or after treatment with immune checkpoint inhibitors (ICIs). Pembrolizumab and lenvatinib are active as monotherapies in RCC; thus, we aimed to evaluate the combination of lenvatinib plus pembrolizumab in these patients. METHODS: We report results of the metastatic RCC cohort from an open-label phase 1b/2 study of lenvatinib plus pembrolizumab in patients aged at least 18 years with selected solid tumours and an Eastern Cooperative Oncology Group performance status of 0-1. Oral lenvatinib at 20 mg was given once daily along with intravenous pembrolizumab at 200 mg once every 3 weeks. Patients remained on study drug treatment until disease progression, development of unacceptable toxicity, or withdrawal of consent. Efficacy was analysed in patients with clear cell metastatic RCC receiving study drug by previous therapy grouping: treatment naive, previously treated ICI naive (previously treated with at least one line of therapy but not with an anti-PD-1 or anti-PD-L1 ICI), and ICI pretreated (ie, anti-PD-1 or anti-PD-L1) patients. Safety was analysed in all enrolled and treated patients. The primary endpoint was the objective response rate at week 24 per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) by investigator assessment. This trial is registered with ClinicalTrials.gov (NCT02501096) and with the EU Clinical Trials Register (EudraCT2017-000300-26), and is closed to new participants. FINDINGS: Between July 21, 2015, and Oct 16, 2019, 145 patients were enrolled in the study. Two patients had non-clear cell RCC and were excluded from the efficacy analysis (one in the treatment-naive group and one in the ICI-pretreated group); thus, the population evaluated for efficacy comprised 143 patients (n=22 in the treatment-naive group, n=17 in the previously treated ICI-naive group, and n=104 in the ICI-pretreated group). All 145 enrolled patients were included in the safety analysis. The median follow-up was 19·8 months (IQR 14·3-28·4). The number of patients with an objective response at week 24 by irRECIST was 16 (72·7%, 95% CI 49·8-89·3) of 22 treatment-naive patients, seven (41·2%, 18·4-67·1) of 17 previously treated ICI-naive patients, and 58 (55·8%, 45·7-65·5) of 104 ICI-pretreated patients. Of 145 patients, 82 (57%) had grade 3 treatment-related adverse events and ten (7%) had grade 4 treatment-related adverse events. The most common grade 3 treatment-related adverse event was hypertension (30 [21%] of 145 patients). Treatment-related serious adverse events occurred in 36 (25%) patients, and there were three treatment-related deaths (upper gastrointestinal haemorrhage, sudden death, and pneumonia). INTERPRETATION: Lenvatinib plus pembrolizumab showed encouraging antitumour activity and a manageable safety profile and might be an option for post-ICI treatment of metastatic RCC. FUNDING: Eisai and Merck Sharp & Dohme.

Variability in ITS1 and ITS2 sequences of historic herbaria and extant (fresh) Phalaris species (Poaceae).

BACKGROUND: Phalaris species (Poaceae) occupy diverse environments throughout all continents except Antarctica. Phalaris arundinacea is an important forage, ornamental, wetland restoration and biofuel crop grown globally as well as being a wetland invasive. The nuclear ribosomal internal transcribed spacer (ITS) region has been used for Phalaris barcoding as a DNA region with high nucleotide diversity for Phalaris species identification. Recent findings that P. arundinacea populations in Minnesota USA are most likely native and not European prompted this analysis to determine whether Eurasian vs. native North American P. arundinacea differed in ITS regions. Our objectives were to amplify and compare ITS regions (ITS1 and ITS2) of historic herbaria (1882-2001) and extant (fresh) Phalaris specimens; analyze ITS regions for species-specific polymorphisms (diagnostic SNPs) and compare ITS regions of historic Phalaris specimens with known, extant Phalaris species. RESULTS: We obtained complete ITS1 and ITS2 sequences from 31 Phalaris historic (herbaria samples, 1908 to 2001) and five extant (fresh) specimens. Herbaria Phalaris specimens did not produce new SNPs (single nucleotide polymorphisms) not present in extant specimens. Diagnostic SNPs were identified in 8/12 (66.6%) Phalaris species. This study demonstrates the use of herbaria tissue for barcoding as a means for improved species identification of Phalaris herbaria specimens. No significant correlation between specimen age and genomic DNA concentration was found. Phalaris arundinacea showed high SNP variation within its clade, with the North American being distinctly different than other USA and most Eurasian types, potentially allowing for future identification of specific SNPs to geographic origin. CONCLUSIONS: While not as efficient as extant specimens to obtain DNA, Phalaris herbaria specimens can produce high quality ITS sequences to evaluate historic genetic resources and facilitate identification of new species-specific barcodes. No correlation between DNA concentration and age of historic samples (119 year range) occurred. Considerable polymorphism was exhibited in the P. arundinacea clade with several N. American accessions being distinct from Eurasian types. Further development of within species- and genus-specific barcodes could contribute to designing PCR primers for efficient and accurate identification of N. American P. arundinacea. Our finding of misidentified Phalaris species indicates the need to exercise stringent quality control measures on newly generated sequence data and to approach public sequence databases in a critical way.

Newly discovered cichlid fish biodiversity threatened by hybridization with non-native species.

Invasive freshwater fishes are known to readily hybridize with indigenous congeneric species, driving loss of unique and irreplaceable genetic resources. Here we reveal that newly discovered (2013-2016) evolutionarily significant populations of Korogwe tilapia (Oreochromis korogwe) from southern Tanzania are threatened by hybridization with the larger invasive Nile tilapia (Oreochromis niloticus). We use a combination of morphology, microsatellite allele frequencies and whole genome sequences to show that O. korogwe from southern lakes (Nambawala, Rutamba and Mitupa) are distinct from geographically disjunct populations in northern Tanzania (Zigi River and Mlingano Dam). We also provide genetic evidence of O. korogwe × niloticus hybrids in three southern lakes and demonstrate heterogeneity in the extent of admixture across the genome. Finally, using the least admixed genomic regions we estimate that the northern and southern O. korogwe populations most plausibly diverged ~140,000 years ago, suggesting that the geographical separation of the northern and southern groups is not a result of a recent translocation, and instead these populations represent independent evolutionarily significant units. We conclude that these newly discovered and phenotypically unique cichlid populations are already threatened by hybridization with an invasive species, and propose that these irreplaceable genetic resources would benefit from conservation interventions.

Adipose Tissue T Regulatory Cells: Implications for Health and Disease.

Obesity dramatically increases the risk of numerous conditions, including type 2 diabetes mellitus and other components of the metabolic syndrome. Pro-inflammatory changes that occur in adipose tissue are critical to the pathogenesis of these obesity-induced complications. Adipose tissue is one of the body's largest endocrine organs, and the cells that comprise the adipose tissue immunoenvironment secrete multiple factors (including adipokines and cytokines) that impact systemic metabolism. In particular, immunosuppressive regulatory T cells (Tregs) decline in obesity, partly in response to its complex interaction with adipocytes, and this decline contributes to disruption of the typical homeostasis observed in lean adipose tissue. Although the regulation of Treg differentiation, function, and enrichment is incompletely understood, factors including various cell-surface co-stimulatory molecules, certain lipid species, and cytokines such as PPARγ, adiponectin, and leptin are important mediators. It is also clear that there may be depot-specific differences in Tregs, rendering adipose tissue Tregs distinct from lymphoid or circulating Tregs, with implications on maintenance and functionality. While most of these findings are derived from studies in murine models, comparatively little is known about the human adipose tissue Treg signature, which requires further investigation.

Heparin Enriched-WPI Coating on Ti6Al4V Increases Hydrophilicity and Improves Proliferation and Differentiation of Human Bone Marrow Stromal Cells.

Titanium alloy (Ti6Al4V) is one of the most prominent biomaterials for bone contact because of its ability to bear mechanical loading and resist corrosion. The success of Ti6Al4V implants depends on bone formation on the implant surface. Hence, implant coatings which promote adhesion, proliferation and differentiation of bone-forming cells are desirable. One coating strategy is by adsorption of biomacromolecules. In this study, Ti6Al4V substrates produced by additive manufacturing (AM) were coated with whey protein isolate (WPI) fibrils, obtained at pH 2, and heparin or tinzaparin (a low molecular weight heparin LMWH) in order to improve the proliferation and differentiation of bone-forming cells. WPI fibrils proved to be an excellent support for the growth of human bone marrow stromal cells (hBMSC). Indeed, WPI fibrils were resistant to sterilization and were stable during storage. This WPI-heparin-enriched coating, especially the LMWH, enhanced the differentiation of hBMSC by increasing tissue non-specific alkaline phosphatase (TNAP) activity. Finally, the coating increased the hydrophilicity of the material. The results confirmed that WPI fibrils are an excellent biomaterial which can be used for biomedical coatings, as they are easily modifiable and resistant to heat treatments. Indeed, the already known positive effect on osteogenic integration of WPI-only coated substrates has been further enhanced by a simple adsorption procedure.

Attenuation of the Köhler Effect in Racially Dissimilar Partnered Exercise Reversed Using Team Identity Strategy.

The authors describe two research experiments exploring the influence of race on the Köhler motivation gain effect with exercise tasks. Experiment 1 tested whether partner racial dissimilarity affects individual performance. Experiment 2 created a team identity recategorization intervention to potentially counter the influence on performance observed in Experiment 1. White male participants were partnered with either a Black or Asian partner (Experiment 1) or with a Black partner utilizing team names and shirt colors as a team identity recategorization strategy (Experiment 2). Racially dissimilar dyads completed two sets of abdominal plank exercises with a Köhler conjunctive task paradigm (stronger partner; team performance outcome dependent upon the weaker-ability participant's performance). The results of Experiment 1 suggest attenuation of the previously successful group motivation gain effect in the racially dissimilar condition. The simple recategorization strategy utilized in Experiment 2 appeared to reverse motivation losses under conjunctive-task conditions in racially dissimilar exercise dyads.

Updating an empirical investigating risk perceptions associated with national ID cards in the wake of the global Covid-19 pandemic.

National ID cards have been debated for some time, especially with the recent Covid-19 global pandemic and increases in technological capabilities, coupled with the need for higher national security. This paper is an empirical extension of Smith's work but in light of the current economic and political turmoil. These differences were inspected from a gender perspective, but the distrust was generally universal. As the beneficial reasons why National ID cards should be implemented (e.g., enhanced security, convenience, and enhancing CRM concepts), still many professionals exhibit numerous fears and are concerned with the risks involved.

A global plastid phylogeny of the fern genus Asplenium (Aspleniaceae).

The infrageneric relationships and taxonomy of the largest fern genus, Asplenium (Aspleniaceae), have remained poorly understood. Previous studies have focused mainly on specific species complexes involving a few or dozens of species only, or have achieved a large taxon sampling but only one plastid marker was used. In the present study, DNA sequences from six plastid markers (atpB, rbcL, rps4, rps4-trnS, trnL and trnL-F) of 1030 accessions (616 of them newly sequenced here) representing c. 420 species of Asplenium (60% of estimated species diversity), 16 species of Hymenasplenium, three Diplaziopsidaceae, and four Rhachidosoraceae were used to produce the largest genus-level phylogeny yet for ferns. Our major results include: (i) Asplenium as broadly circumscribed is monophyletic based on our inclusion of representatives of 32 of 38 named segregate genera; (ii) 11 major clades in Asplenium are identified, and their relationships are mostly well-resolved and strongly supported; (iii) numerous species, unsampled in previous studies, suggest new relationships and numerous cryptic species and species complexes in Asplenium; and (iv) the accrued molecular evidence provides an essential foundation for further investigations of complex patterns of geographical diversification, speciation and reticulate evolution in this family.