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Salinity gradients act as strong environmental barriers that limit the distribution of aquatic organisms. Changes in gene expression associated with transitions between freshwater and saltwater environments can provide insights into organismal responses to variation in salinity. We used RNA-sequencing (RNA-seq) to investigate genome-wide variation in gene expression between a hypersaline population and a freshwater population of the livebearing fish species Limia perugiae (Poeciliidae). Our analyses of gill gene expression revealed potential molecular mechanisms underlying salinity tolerance in this species, including the enrichment of genes involved in ion transport, maintenance of chemical homeostasis, and cell signaling in the hypersaline population. We also found differences in gene expression patterns associated with cell-cycle and protein-folding processes between the hypersaline and freshwater L. perugiae. Bidirectional freshwater-saltwater transitions have occurred repeatedly during the diversification of fishes, allowing for broad-scale examination of repeatable patterns in evolution. Therefore, we compared transcriptomic variation in L. perugiae with other teleosts that have made freshwater-saltwater transitions to test for convergence in gene expression. Among the four distantly related population pairs from high- and low-salinity environments that we included in our analysis, we found only ten shared differentially expressed genes, indicating little evidence for convergence. However, we found that differentially expressed genes shared among three or more lineages were functionally enriched for ion transport and immune functioning. Overall, our results—in conjunction with other recent studies—suggest that different genes are involved in salinity transitions across disparate lineages of teleost fishes. [ABSTRACT FROM AUTHOR]

Do economic shocks increase labor market inequalities between immigrants and natives? The COVID-19 crisis reduced economic activity for almost all social groups, providing a recent case for answering this question. Research tends to focus on employment levels, overlooking potential inequalities in other job characteristics. Workers in Germany have largely kept their jobs, although their working hours were reduced. Using German high-frequency survey data, we analyze whether there was a difference in the reduction of hours for immigrants and immigrants' descendants (IAD) compared to natives. Since IAD are overrepresented in both heavily affected and essential jobs, we argue that the effects may be heterogeneous across the distribution of the change in hours. As merely comparing averages would ignore this heterogeneity, we employ OLS and quantile treatment effect estimations to analyze working hours changes in the early COVID-19 crisis. Results show that IAD reduced hours more than natives. This effect is particularly pronounced at the lower end of the distribution of the change in working hours. Our findings suggest that IAD experienced economic hardship more often than natives and corroborate earlier findings of increased immigrant-native inequalities in times of crisis. This calls for further investigation of policies aimed at protecting vulnerable groups. [ABSTRACT FROM AUTHOR]

This is a single arm, open label perioperative trial to assess the feasibility, pharmacokinetics and pharmacodynamics of treatment with safusidenib following biopsy, and prior to surgical resection in patients with IDH1 mutated glioma who have not received radiation therapy or chemotherapy. Fifteen participants will receive treatment in two parts. First, biopsy followed by one cycle (28 days) of safusidenib, an orally available, small molecular inhibitor of mutated IDH1, then maximal safe resection of the tumor (Part A). Second, after recovery from surgery, safusidenib until disease progression or unacceptable toxicity (Part B). This research will enable objective measurement of biological activity of safusidenib in patients with IDH1 mutated glioma. Anti-tumor activity will be assessed by progression free survival and time to next intervention. Clinical Trial Registration:NCT05577416 (ClinicalTrials.gov) Plain Language Summary Adult low-grade gliomas (aLGG) are primary brain cancers, defined by mutations in IDH1 or IDH2. When the IDH gene becomes abnormal (mutated), production of a metabolite that causes cancer cells to grow is increased. These tumors grow slowly but invade the normal functioning brain, making them nearly impossible to cure. The current standard of care treatment includes surgery, followed by radiation therapy and chemotherapy, the timing of which depends on the risk of cancer regrowth. Some patients may be suitable for monitoring with MRI scans alone, however recurrences will inevitably occur. Recently developed targeted mutant IDH inhibitors for aLGG patients may be beneficial both at diagnosis and recurrence. Notably, early treatment prior to radiation therapy and chemotherapy delays growth of aLGG and the need for subsequent radiation therapy and chemotherapy. Nevertheless, most patients will eventually suffer further tumor growth and the optimal timing and sequencing of these therapies remains an area of active research. This research investigates the mutant IDH1 inhibitor safusidenib. The researchers are conducting an innovative clinical trial where patients with aLGG, who have not received radiation therapy or chemotherapy, are treated with safusidenib following a biopsy and prior to surgical removal of their tumor. In this study they investigate whether this trial design is safe and feasible, and how safusidenib works; with the goal to better understand the optimal use of IDH inhibitors for patients with aLGG. Article highlights Introduction Background & rationale Adult low-grade gliomas (aLGGs) are defined by IDH1/2 mutations which lead to accumulation of 2-HG, an oncometabolite affecting tumorigenesis. 2-HG inhibits α-KG-dependent enzymes, affecting epigenetic regulation, collagen synthesis and cell signaling, hindering progenitor cell differentiation and promoting cancer. In addition, 2-HG promotes angiogenesis, an immunosuppressive tumor microenvironment and oxidative damage. aLGGs grow slowly, diffusely infiltrating the brain and are difficult to cure. Emergence of targeted mutant IDH inhibitors has shifted focus toward identifying prognostic markers and future combination studies. Current treatment of aLGG Treatment includes maximal safe surgical resection, radiation therapy and sequential chemotherapy. Early, extensive surgery improves overall survival. Active surveillance with MRI is suitable for some patients to delay side effects. Mutant IDH inhibitors for glioma Multiple mutant IDH inhibitors have shown promise in glioma. Vorasidenib (IDH1/2 inhibitor) improved progression-free survival in the INDIGO Phase III trial. Safusidenib (DS-1001b, AB-218) is an orally available small molecule inhibitor of mutant IDH1 with demonstrated brain penetration and clinical activity in Phase I trials. Perioperative trials There have been few therapeutic advances in glioma due to challenges in measuring drug penetration and pharmacodynamic (PD) evaluation. Perioperative trials, including biopsy to obtain pre-treatment tissue, are feasible and offer a means to examine the direct effects of new drugs. These studies allow evaluation of drug pharmacokinetics (PK) and PD outcomes. Objectives Hypothesis: Treatment with safusidenib following biopsy and prior to resection in newly diagnosed IDH1 mutated glioma is feasible. Estimate: >60% of screened patients completing planned investigations and procedures. Primary objective: Assess feasibility and acceptability of a perioperative study in IDH1 mutated aLGG patients. Secondary end points: Determine safusidenib toxicity, safety of two-stage surgery and biological activity by changes in 2-HG levels. Methods Participants, interventions, & outcomes Key inclusion: Adults ≥18 years with aLGG diagnosis not requiring urgent resection. Key exclusion: prior chemotherapy/radiation, cerebellar/brainstem tumors. Procedures: Open biopsy, oral safusidenib, second-stage resection, continued safusidenib post-resection. Data collection: tumor tissue, CSF and blood samples processed per protocols. PK/PD relationships: Evaluated by blood, tumor and CSF samples. Biological activity: Assessed by changes in 2-HG levels and IDH1 ctDNA. Data collection, management, & analysis Tumor tissue, CSF and blood samples collected for research. Safusidenib PK will be investigated to evaluate PK/PD relationships. Translational end points include paired whole-genome transcriptome profiling, single nuclei RNA sequencing, bulk metabolomics and DNA methylation. Spatial transcriptomics using in situ digital sequencing and spatial metabolomics on sections pre- and post-safusidenib treatment. Descriptive statistics for demographics, safety, PK, PD, efficacy and biomarker data by dose and time. Monitoring Toxicity: Monitored by adverse events, clinical tests and vital signs. Safety of surgery: 30-day morbidity and mortality recorded post-biopsy and resection. Radiological response: Determined by MRI changes and LGG-RANO criteria. Progression-free survival and time to treatment failure: Calculated from biopsy date. Conclusion Perioperative studies in aLGG offer a unique opportunity to study drug effects and are feasible, ethical and acceptable to patients. [ABSTRACT FROM AUTHOR]

Atrial arrhythmias are an important cause of morbidity and mortality in adults with congenital heart disease (ACHD). In acquired heart disease, the left atrial (LA) strain has been shown to predict supraventricular tachyarrhythmias (SVT). This study aimed to investigate whether reduced LA strain is associated with SVT in ACHD patients. This retrospective, single-center cohort study collected baseline clinical and echocardiographic data of 206 ACHD patients (157 left heart defect, 49 right heart defect). Patients with sinus rhythm at baseline and a 5-year follow-up (median age 29, IQR 22–41 years) were included. Diagnosis of sustained SVT was determined from clinical reports during the follow-up period. New or recurrent sustained SVT occurred in 16 patients (7.8%, median follow-up of 6.2 years). Patients who developed SVT were older, more likely to have diastolic dysfunction, and had larger LA dimensions, left ventricular mass, and a lower peak LA longitudinal strain (PALS). Lower PALS was associated with higher risk of SVT in patients with left and right heart defects. Patients in the lowest quartile for PALS had a 15.9-fold higher hazard ratio of SVT (95% confidence interval, 4.5 to 56.0, p < 0.001) in comparison with the top three quartiles. PALS provides information about the occurrence of SVT in the ACHD population. Including measurement of LA strain in the follow-up of these patients may allow to better identify patients at risk of future atrial arrhythmias. [ABSTRACT FROM AUTHOR]

Air quality is of large concern in the city of Krakow, southern Poland. A comprehensive study was launched by us in which two PM fractions (PM1 and PM10) were sampled during 1-year campaign, lasting from April 21, 2018 to March 19, 2019. A suite of modern analytical methods was used to characterize the chemical composition of the collected samples. The contents of 14 sugars, sugar alcohols and anhydrosugars, 16 polycyclic aromatic hydrocarbons, selected metals and non-metals and ions were analyzed, in addition to organic and elemental carbon content. The carbon isotope composition in both analysed PM fractions, combined with an isotope-mass balance method, allowed to distinguish three main components of carbonaceous emissions in the city: (1) emissions related to combustion of hard coal, (2) emissions related to road transport, and (3) biogenic emissions. The heating season emissions from coal combustion had the biggest contribution to the reservoir of carbonaceous aerosols in the PM10 fraction (44%) and, together with the biogenic emission, they were the biggest contributors to the PM1 fraction (41% and 44%, respectively). In the non-heating season, the dominant source of carbon in PM10 and PM1 fraction were the biogenic emissions (48 and 54%, respectively). [ABSTRACT FROM AUTHOR]

To better understand the physiological basis of obesity in women, we investigated whether obesity or menstrual cycle phase affects laboratory test-meal size or meal-stimulated plasma cholecystokinin (CCK) concentration. Women with healthy weight (body mass index [BMI] of 18.5-24.9 kg/m2, N = 16) or obesity (BMI 30-39.9 kg/m2, N = 20) were tested once in the late-follicular or peri-ovulatory phase (LF/PO) and once in the mid-luteal phase (ML). Meals of ham sandwiches were offered and blood was sampled. Menstrual cycle phases were verified with participants' reports of menses and measurements of progesterone and luteinizing hormone (LH) concentrations. Women with obesity ate significantly larger meals than women with healthy weight, (mean, 711 [95% CI, 402-1013] kJ, P = 0.001, during the LF/PO and 426 [105-734] kJ, P = 0.027, larger during the ML). Women with healthy weight ate smaller meals during LF/PO than ML (decrease, 510 [192-821 kJ], P = 0.008), but women with obesity did not (decrease, 226 [−87-542] kJ, P = 0.15). CCK concentrations 18 to 30 minutes after meal onset were lower in women with obesity than in women with healthy weight during LF/PO (3.6 [3.1-4.1] vs 6.1 [4.5-7.7] pmol/L; P = 0.004), but not during ML, with a significant interaction effect (1.8 [1.2-2.4] pmol/L, P = 0.048). Women with obesity consumed larger meals than women with healthy weight but displayed reduced meal-stimulated plasma CCK concentrations. These data are consistent with the hypothesis that a defect in CCK secretion compromises satiation in obese women and contributes to the development or maintenance of obesity. [ABSTRACT FROM AUTHOR]

Representing the probability and uncertainty of outcomes facilitates adaptive behavior by allowing organisms to prepare in advance and devote attention to relevant events. Probability and uncertainty are often studied only for valenced (appetitive or aversive) outcomes, raising the question of whether the identified neural machinery also processes the probability and uncertainty of motivationally neutral outcomes. Here, we aimed to dissociate valenced from valence-independent (i.e., generic) probability (p; maximum at p = 1) and uncertainty (maximum at p = 0.5) signals using human neuroimaging. In a Pavlovian task (n = 41; 19 females), different cues predicted appetitive, aversive, or neutral liquids with different probabilities (p= 0, p = 0.5, p = 1). Cue-elicited motor responses accelerated, and pupil sizes increased primarily for cues that predicted valenced liquids with higher probability. For neutral liquids, uncertainty rather than probability tended to accelerate cue-induced responding and decrease pupil size. At the neural level, generic uncertainty signals were limited to the occipital cortex, while generic probability also activated the anterior ventromedial prefrontal cortex. These generic probability and uncertainty signals contrasted with cue-induced responses that only encoded the probability and uncertainty of valenced liquids in medial prefrontal, insular, and occipital cortices. Our findings show a behavioral and neural dissociation of generic and valenced signals. Thus, some parts of the brain keep track of motivational charge while others do not, highlighting the need and usefulness of characterizing the exact nature of learned representations. [ABSTRACT FROM AUTHOR]

Dingoes are culturally and ecologically important free-living canids whose ancestors arrived in Australia over 3,000 B.P., likely transported by seafaring people. However, the early history of dingoes in Australia--including the number of founding populations and their routes of introduction--remains uncertain. This uncertainty arises partly from the complex and poorly understood relationship between modern dingoes and New Guinea singing dogs, and suspicions that post-Colonial hybridization has introduced recent domestic dog ancestry into the genomes of many wild dingo populations. In this study, we analyzed genome-wide data from nine ancient dingo specimens ranging in age from 400 to 2,746 y old, predating the introduction of domestic dogs to Australia by European colonists. We uncovered evidence that the continent-wide population structure observed in modern dingo populations had already emerged several thousand years ago. We also detected excess allele sharing between New Guinea singing dogs and ancient dingoes from coastal New South Wales (NSW) compared to ancient dingoes from southern Australia, irrespective of any post-Colonial hybrid ancestry in the genomes of modern individuals. Our results are consistent with several demographic scenarios, including a scenario where the ancestry of dingoes from the east coast of Australia results from at least two waves of migration from source populations with varying affinities to New Guinea singing dogs. We also contribute to the growing body of evidence that modern dingoes derive little genomic ancestry from post-Colonial hybridization with other domestic dog lineages, instead descending primarily from ancient canids introduced to Sahul thousands of years ago. [ABSTRACT FROM AUTHOR]

Adaptive coding of reward is the process by which neurons adapt their response to the context of available compensations. Higher rewards lead to a stronger brain response, but the increase of the response depends on the range of available rewards. A steeper increase is observed in a narrow range and a more gradual slope in a wider range. In schizophrenia, adaptive coding appears to be affected in different domains, especially in the reward domain. Here, we tested adaptive coding of reward in a large group of patients with schizophrenia (n = 86) and control subjects (n = 66). We assessed: (i) the association between adaptive coding deficits and symptoms; (ii) the longitudinal stability of deficits (the same task was performed 3 months apart); and (iii) the stability of results between two experimental sites. We used functional MRI and the monetary incentive delay task to assess adaptation of participants to two different reward ranges: a narrow range and a wide range. We used a region-of-interest analysis to evaluate adaptation within striatal and visual regions. Patients and control subjects underwent a full demographic and clinical assessment. We found reduced adaptive coding in patients, with a decreased slope in the narrow reward range with respect to that of control participants, in striatal but not visual regions. This pattern was observed at both research sites. Upon retesting, patients increased their narrow-range slopes, showing improved adaptive coding, whereas control subjects slightly reduced them. At retesting, patients with overly steep slopes in the narrow range also showed higher levels of negative symptoms. Our data confirm deficits in reward adaptation in schizophrenia and reveal an effect of practice in patients, leading to improvement, with steeper slopes upon retesting. However, in some patients, an excessively steep slope may result in poor discriminability of larger rewards, owing to early saturation of the brain response. Together, the loss of precision of reward representation in new (first exposure, underadaptation) and more familiar (retest, overadaptation) situations might contribute to the multiple motivational symptoms in schizophrenia. [ABSTRACT FROM AUTHOR]

Aims: Data on diuretic use in pregnancy are limited and inconsistent, and consequently it remains unclear whether they can be used safely. Our study aims to evaluate the perinatal outcomes after in‐utero diuretic exposure. Methods and results: The Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with heart disease. Outcomes were compared between women who used diuretics during pregnancy versus those who did not. Multivariable regression analysis was used to assess the impact of diuretic use on the occurrence of congenital anomalies and foetal growth. Diuretics were used in 382 (6.7%) of the 5739 ROPAC pregnancies, most often furosemide (86%). Age >35 years (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2–2.0), other cardiac medication use (OR 5.4, 95% CI 4.2–6.9), signs of heart failure (OR 1.7, 95% CI 1.2–2.2), estimated left ventricular ejection fraction <40% (OR 2.9, 95% CI 2.0–4.2), New York Heart Association class >II (OR 3.4, 95% CI 2.3–5.1), valvular heart disease (OR 6.3, 95% CI 4.7–8.3) and cardiomyopathy (OR 3.9, 95% CI 2.6–5.7) were associated with diuretic use during pregnancy. In multivariable analysis, diuretic use during the first trimester was not significantly associated with foetal or neonatal congenital anomalies (OR 1.3, 95% CI 0.7–2.6), and diuretic use during pregnancy was also not significantly associated with small for gestational age (OR 1.4, 95% CI 1.0–1.9). Conclusions: Our study does not conclusively establish an association between diuretic use during pregnancy and adverse foetal outcomes. Given these findings, it is essential to assess the risk–benefit ratio on an individual basis to guide clinical decisions. [ABSTRACT FROM AUTHOR]

The Journal of Avian Biology (JAB) publishes high-quality research on birds' ecology, evolution, and behavior from around the world. To provide a more nimble format for publishing overviews in avian biology, JAB introduced the 'mini-review' article category in 2022. The journal also established the 'JAB review award' to recognize exceptional mini-review manuscripts from early career researchers, with winners receiving a 1000€ honorarium. The competition aims to highlight new developments in avian research and encourage submissions from underrepresented groups and geographic areas. [Extracted from the article]

Purpose: The aim of this in-vitro study was to investigate the antimicrobial efficacy of identical experimental toothpastes with different stannous sources. Materials and Methods: Streptococcus mutans biofilms were grown on protein-coated glass disks in static conditions for 24 h and thereafter exposed to toothpaste slurries or physiological saline (negative control; n = 15) for 30 s. Four experimental toothpastes were applied in this study, containing either stannous chloride (SnCl2; B: 3500 ppm Sn2+, and D: 3600 ppm Sn2+) or stannous fluoride (SnF2; C: 3500 ppm Sn2+, and E: 3600 ppm Sn2+). Marketed toothpaste meridol® (A: 3300 ppm SnF2) served as control. All five toothpastes contained amine fluoride (AmF). The biofilms were placed on agar surface and their metabolic activity was assessed by isothermal microcalorimetry over 96 h. The heat flow data was analysed for growth rate and lag time using grofit package in software R. Additionally, reduction of active biofilm compared to untreated control was calculated. Results: All toothpastes significantly prolong the lag time of treated biofilms in comparison to negative control (p < 0.05). Toothpastes containing SnF2 (C and E) prolonged the lag time statistically significantly compared to toothpastes containing SnCl2 (B and D) (p < 0.05). The maximum growth rate was statistically significantly reduced by all tested toothpastes compared to the untreated control group (p < 0.05). Toothpastes containing SnF2 (A, C and E) reached 59.9 ± 7.8, 61.9 ± 7.7, and 55.6 ± 7.0% reduction of active biofilm, respectively. Thus, they exhibit statistically significantly better results than toothpastes B (52.9 ± 9.9%) and D (44.7 ± 7.6%). Toothpaste D, which contains a slightly higher concentration of Sn2+, was the least effective in reducing active biofilm. Conclusion: The toothpastes containing SnF2 combined with AmF had the highest antimicrobial efficacy in this study. [ABSTRACT FROM AUTHOR]

Regulating transcription allows organisms to respond to their environment, both within a single generation (plasticity) and across generations (adaptation). We examined transcriptional differences in gill tissues of fishes in the Poecilia mexicana species complex (family Poeciliidae), which have colonized toxic springs rich in hydrogen sulfide (H2S) in southern Mexico. There are gene expression differences between sulfidic and non-sulfidic populations, yet regulatory mechanisms mediating this gene expression variation remain poorly studied. We combined capped-small RNA sequencing (csRNA-seq), which captures actively transcribed (i.e. nascent) transcripts, and messenger RNA sequencing (mRNA-seq) to examine how variation in transcription, enhancer activity, and associated transcription factor binding sites may facilitate adaptation to extreme environments. csRNA-seq revealed thousands of differentially initiated transcripts between sulfidic and non-sulfidic populations, many of which are involved in H2S detoxification and response. Analyses of transcription factor binding sites in promoter and putative enhancer csRNA-seq peaks identified a suite of transcription factors likely involved in regulating H2S-specific shifts in gene expression, including several key transcription factors known to respond to hypoxia. Our findings uncover a complex interplay of regulatory processes that reflect the divergence of extremophile populations of P. mexicana from their non-sulfidic ancestors and suggest shared responses among evolutionarily independent lineages. [ABSTRACT FROM AUTHOR]

Natural environments vary, and organisms cope with this variation in two general ways: local adaptation and phenotypic plasticity, although these strategies often overlap and interact. This study explored how local adaptation, phenotypic plasticity, and their interactions shaped phenotypic variation in populations of Poecilia mexicana, an extremophile fish living in adjacent but ecologically divergent habitats. By comparing populations from the wild with fish raised in a common-garden environment, we evaluated how genetic differentiation between populations and plasticity contributed to the phenotypic variation observed in nature. We quantified variation in the size of six organs (brain, eyes, gills, heart, liver, and gastrointestinal tract), routine metabolic rate, and body shape. We found evidence for genetic differences between populations impacting the expression of the majority of traits, in addition to or in interaction with phenotypic plasticity and other predictor variables. Overall, our results suggest that trait divergence between populations was at least in part driven by evolutionary change and not just merely by plasticity induced by environmental differences between habitats. Future studies will have to rigorously test whether evolutionary divergence was caused by natural selection and what traits represent adaptations to the different ecological conditions. [ABSTRACT FROM AUTHOR]

From deciding which meal to prepare for our guests to trading off the proenvironmental effects of climate protection measures against their economic costs, we often must consider the consequences of our actions for the well-being of others (welfare). Vexingly, the tastes and views of others can vary widely. To maximize welfare according to the utilitarian philosophical tradition, decision-makers facing conflicting preferences of others should choose the option that maximizes the sum of the subjective value (utility) of the entire group. This notion requires comparing the intensities of preferences across individuals. However, it remains unclear whether such comparisons are possible at all and (if they are possible) how they might be implemented in the brain. Here, we show that female and male participants can both learn the preferences of others by observing their choices and represent these preferences on a common scale to make utilitarian welfare decisions. On the neural level, multivariate support vector regressions revealed that a distributed activity pattern in the ventromedial prefrontal cortex (VMPFC), a brain region previously associated with reward processing, represented the preference strength of others. Strikingly, also the utilitarian welfare of others was represented in the VMPFC and relied on the same neural code as the estimated preferences of others. Together, our findings reveal that humans can behave as if they maximized utilitarian welfare using a specific utility representation and that the brain enables such choices by repurposing neural machinery processing the reward others receive. [ABSTRACT FROM AUTHOR]

Adaptation to extreme environments often involves the evolution of dramatic physiological changes. To better understand how organisms evolve these complex phenotypic changes, the repeatability and predictability of evolution, and possible constraints on adapting to an extreme environment, it is important to understand how adaptive variation has evolved. Poeciliid fishes represent a particularly fruitful study system for investigations of adaptation to extreme environments due to their repeated colonization of toxic hydrogen sulfide–rich springs across multiple species within the clade. Previous investigations have highlighted changes in the physiology and gene expression in specific species that are thought to facilitate adaptation to hydrogen sulfide–rich springs. However, the presence of adaptive nucleotide variation in coding and regulatory regions and the degree to which convergent evolution has shaped the genomic regions underpinning sulfide tolerance across taxa are unknown. By sampling across seven independent lineages in which nonsulfidic lineages have colonized and adapted to sulfide springs, we reveal signatures of shared evolutionary rate shifts across the genome. We found evidence of genes, promoters, and putative enhancer regions associated with both increased and decreased convergent evolutionary rate shifts in hydrogen sulfide–adapted lineages. Our analysis highlights convergent evolutionary rate shifts in sulfidic lineages associated with the modulation of endogenous hydrogen sulfide production and hydrogen sulfide detoxification. We also found that regions with shifted evolutionary rates in sulfide spring fishes more often exhibited convergent shifts in either the coding region or the regulatory sequence of a given gene, rather than both. [ABSTRACT FROM AUTHOR]

Livebearing fishes (Poeciliidae) have been used as models to test several aspects of life history theory. Previous work in these fishes showed that traits such as age and size at maturity, reproductive allocation, and number and size of offspring can each be shaped by natural selection. Life history traits can also be influenced by the environment, and in some cases, such phenotypic plasticity can also be adaptive. Resource availability in the environment can affect life history trait expression with increased resources expected to result in increased investment in reproduction. Here, we test this hypothesis in the Costa Rican livebearing fish Priapichthys annectens by quantifying life history traits and comparing trait values between populations collected during the dry season versus the wet season, periods when resource availability varies. We found that life history traits related to reproductive investment, but not the timing of reproductive events, differed between seasons. During the wet season, female body condition increased, and females invested less in reproduction, having fewer but larger offspring. Irrespective of the season, larger females gave birth to larger offspring. Finally, we found that this species utilizes a lecithotrophic strategy of provisioning eggs with nutrients being deposited in the ova prior to fertilization, and that females only carry one developing brood at a time (no superfetation). This is the first study documenting the life history of P. annectens , and it adds to a growing body of work suggesting that seasonal environmental differences can induce changes in the expression of some—but not all—life history traits. [ABSTRACT FROM AUTHOR]

The oxidative potential (OP) of particulate matter (PM) is a major driver of PMassociated health effects. In India, the emission sources defining PM-OP, and their local/regional nature, are yet to be established. Here, to address this gap we determine the geographical origin, sources of PM, and its OP at five IndoGangetic Plain sites inside and outside Delhi. Our findings reveal that although uniformly high PM concentrations are recorded across the entire region, local emission sources and formation processes dominate PM pollution. Specifically, ammonium chloride, and organic aerosols (OA) from traffic exhaust, residential heating, and oxidation of unsaturated vapors from fossil fuels are the dominant PM sources inside Delhi. Ammonium sulfate and nitrate, and secondary OA from biomass burning vapors, are produced outside Delhi. Nevertheless, PM-OP is overwhelmingly driven by OA from incomplete combustion of biomass and fossil fuels, including traffic. These findings suggest that addressing local inefficient combustion processes can effectively mitigate PM health exposure in northern India. [ABSTRACT FROM AUTHOR]

Population genetic simulation has emerged as a common tool for investigating increasingly complex evolutionary and demographic models. Software capable of handling high‐level model complexity has recently been developed, and the advancement of tree sequence recording now allows simulations to merge the efficiency and genealogical insight of coalescent simulations with the flexibility of forward simulations. However, frameworks utilizing these features have not yet been compared and benchmarked. Here, we evaluate various simulation workflows using the coalescent simulator msprime and the forward simulator SLiM, to assess resource efficiency and determine an optimal simulation framework. Three aspects were evaluated: (1) the burn‐in, to establish an equilibrium level of neutral diversity in the population; (2) the forward simulation, in which temporally fluctuating selection is acting; and (3) the final computation of summary statistics. We provide typical memory and computation time requirements for each step. We find that the fastest framework, a combination of coalescent and forward simulation with tree sequence recording, increases simulation speed by over twenty times compared to classical forward simulations without tree sequence recording, although it does require six times more memory. Overall, using efficient simulation workflows can lead to a substantial improvement when modelling complex evolutionary scenarios—although the optimal framework ultimately depends on the available computational resources. [ABSTRACT FROM AUTHOR]

Air quality is of large concern in the city of Krakow, southern Poland. A comprehensive study was launched by us in which two PM fractions (PM1 and PM10) were sampled during 1-year campaign, lasting from April 21, 2018 to March 19, 2019. A suite of modern analytical methods was used to characterize the chemical composition of the collected samples. The contents of 14 sugars, sugar alcohols and anhydrosugars, 16 polycyclic aromatic hydrocarbons, selected metals and non-metals and ions were analyzed, in addition to organic and elemental carbon content. The carbon isotope composition in both analysed PM fractions, combined with an isotope-mass balance method, allowed to distinguish three main components of carbonaceous emissions in the city: (1) emissions related to combustion of hard coal, (2) emissions related to road transport, and (3) biogenic emissions. The heating season emissions from coal combustion had the biggest contribution to the reservoir of carbonaceous aerosols in the PM10 fraction (44%) and, together with the biogenic emission, they were the biggest contributors to the PM1 fraction (41% and 44%, respectively). In the non-heating season, the dominant source of carbon in PM10 and PM1 fraction were the biogenic emissions (48 and 54%, respectively). [ABSTRACT FROM AUTHOR]

Arsenic and silica are known inhibitors of the crystallization of iron minerals from poorly ordered precursor phases. However, little is known about the effects of co-existing As and Si on the crystallization and long-term stability of mixed-valence Fe minerals such as green rust (GR). GR usually forms in anoxic, Fe2+-rich, near-neutral pH environments, where they influence the speciation and mobility of trace elements, nutrients and contaminants. In this work, the Fe2+-induced transformation of As- and/or Si-bearing ferrihydrite (FHY) was monitored at pH 8 ([As]initial = 100 μM, Si/As = 10) over 720 h. Our results showed that in the presence of As(III) + Si or As(V) + Si, GR sulfate (GRSO4) formation from FHY was up to four times slower compared to single species system containing only As(III), As(V) or Si. Co-existing As(III) + Si and As(V) + Si also inhibited GRSO4 transformation to magnetite, contrary to systems with only Si or As(V). Overall, our findings demonstrate the synergistic inhibitory effect of co-existing Si on the crystallization and solid-phase stability of As-bearing GRSO4, establishing an inhibitory effect ladder: As(III) + Si > As(V) + Si > As(III) > Si > As(V). This further highlights the importance of GR in potentially controlling the fate and mobility of As in ferruginous, Si-rich groundwater and sediments such as those in South and Southeast Asia. [ABSTRACT FROM AUTHOR]

The two-process model of sleep regulation has served as a conceptual framework in the last four decades for understanding sleep physiology. In the 1970s, long-term recordings of sleep in rats were obtained thanks to EEG telemetry. NonREM sleep and REM sleep were found to differ in their time course and response to light-dark protocols. There were indications for their coupling to the circadian system, in particular the light-dark and the dark-light transitions. With the advent of quantitative EEG analysis, slow-wave activity in nonREM sleep was recognized as a sleep-wake-dependent variable. The term "sleep homeostasis" was coined to specify the regulated balance between sleep and waking. The regulatory homeostatic process was designated as "Process S". In the two-process model, its interaction with the circadian pacemaker "Process C" can account for sleep duration under various experimental protocols. Local, use-dependent slow-wave activity changes were demonstrated in both humans and rats by the selective, unilateral activation of a cortical region prior to sleep. Finding that rest in invertebrates has sleep-like regulatory properties opened a new realm of animal studies. Comparative sleep studies in a broad variety of animal species confirmed the validity of the basic concepts of the two-process model. Recent studies have addressed sleep-related changes of brain temperature as an indicator of brain metabolism; the application of the model to Drosophila; the divergence of cortical and subcortical states; and sleep in an increasing number of species and taxa. [ABSTRACT FROM AUTHOR]

Theories of moral development propose that empathy is transmitted across individuals. However, the mechanisms through which empathy is socially transmitted remain unclear. Here, we combine computational learning models and functional MRI to investigate whether, and if so, how empathic and non-empathic responses observed in others affect the empathy of female observers. The results of three independent studies showed that watching empathic or non-empathic responses generates a learning signal that respectively increases or decreases empathy ratings of the observer. A fourth study revealed that the learning-related transmission of empathy is stronger when observing human rather than computer demonstrators. Finally, we show that the social transmission of empathy alters empathy-related responses in the anterior insula, i.e., the same region that correlated with empathy baseline ratings, as well as its functional connectivity with the temporoparietal junction. Together, our findings provide a computational and neural mechanism for the social transmission of empathy that accounts for changes in individual empathic responses in empathic and non-empathic social environments. [ABSTRACT FROM AUTHOR]

This letter is a response to a report on the outcomes of flexor tendon repair. The author requests further information on the details of ruptured tendons in 19 patients, specifically regarding the repair methods used and the number of strands in the repairs. The authors of the report provide additional information, stating that most ruptures occurred in zone 2 and were treated with six-strand or four-strand sutures. They also clarify that two-strand repairs were rarely used in their clinics and did not show higher rupture rates compared to four- or six-strand sutures. The report concludes that zone 2 repairs remain technically challenging and require more intensive rehabilitation. [Extracted from the article]

Peru ranks among the three countries with the highest bird species diversity globally and a majority of those species are found in the Peruvian Amazon. However, birds in this area are currently facing serious anthropogenic threats. Genetic and genomic methods are becoming important tools for avian biodiversity monitoring and conservation planning. Comprehensive molecular libraries that are publicly available are key to the effective deployment of these tools. We analyze the information gaps for four molecular markers in the most important genetic sequence databases, Barcode of Life Data Systems (BOLD) and NCBI GenBank, for bird species of the Peruvian Amazonia. We found that 64% of Peruvian Amazonian bird species have gene sequences for COI, 59.5% have CYTB sequences, 16.4% have 12S sequences, and only 0.6% have 18S sequences. However, these numbers decrease drastically to 4.3% for COI sequences when we only consider specimens sampled in Peru. Our data also showed that 43.8% of Peruvian Amazonian endemic species (n = 32) are missing sequences of any screened marker uploaded to GenBank or BOLD. Our results will encourage and guide efforts of the scientific community to complete reference libraries for Peruvian avian species that will be useful for future DNA-based monitoring projects that include birds. [ABSTRACT FROM AUTHOR]

To better understand the physiological basis of obesity in women, we investigated whether obesity or menstrual cycle phase affects laboratory test-meal size or meal-stimulated plasma cholecystokinin (CCK) concentration. Women with healthy weight (body mass index [BMI] of 18.5-24.9 kg/m2, N = 16) or obesity (BMI 30-39.9 kg/m2, N = 20) were tested once in the late-follicular or peri-ovulatory phase (LF/PO) and once in the mid-luteal phase (ML). Meals of ham sandwiches were offered and blood was sampled. Menstrual cycle phases were verified with participants' reports of menses and measurements of progesterone and luteinizing hormone (LH) concentrations. Women with obesity ate significantly larger meals than women with healthy weight, (mean, 711 [95% CI, 402-1013] kJ, P = 0.001, during the LF/PO and 426 [105-734] kJ, P = 0.027, larger during the ML). Women with healthy weight ate smaller meals during LF/PO than ML (decrease, 510 [192-821 kJ], P = 0.008), but women with obesity did not (decrease, 226 [−87-542] kJ, P = 0.15). CCK concentrations 18 to 30 minutes after meal onset were lower in women with obesity than in women with healthy weight during LF/PO (3.6 [3.1-4.1] vs 6.1 [4.5-7.7] pmol/L; P = 0.004), but not during ML, with a significant interaction effect (1.8 [1.2-2.4] pmol/L, P = 0.048). Women with obesity consumed larger meals than women with healthy weight but displayed reduced meal-stimulated plasma CCK concentrations. These data are consistent with the hypothesis that a defect in CCK secretion compromises satiation in obese women and contributes to the development or maintenance of obesity. [ABSTRACT FROM AUTHOR]

Habits pose a fundamental puzzle for those aiming to understand human behavior. They pervade our everyday lives and dominate some forms of psychopathology but are extremely hard to elicit in the lab. In this Registered Report, we developed novel experimental paradigms grounded in computational models, which suggest that habit strength should be proportional to the frequency of behavior and, in contrast to previous research, independent of value. Specifically, we manipulated how often participants performed responses in two tasks varying action repetition without, or separately from, variations in value. Moreover, we asked how this frequency-based habitization related to value-based operationalizations of habit and self-reported propensities for habitual behavior in real life. We find that choice frequency during training increases habit strength at test and that this form of habit shows little relation to value-based operationalizations of habit. Our findings empirically ground a novel perspective on the constituents of habits and suggest that habits may arise in the absence of external reinforcement. We further find no evidence for an overlap between different experimental approaches to measuring habits and no associations with self-reported real-life habits. Thus, our findings call for a rigorous reassessment of our understanding and measurement of human habitual behavior in the lab. [ABSTRACT FROM AUTHOR]

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Telomere length and telomere shortening are thought to be critical cellular attributes and processes that are related to an individual's life span and fitness. The general pattern across most taxa is that after birth telomere length gradually decreases with age. Telomere protection and restoration mechanisms are usually assumed to reduce the rate of shortening or at most keep telomere length constant. However, here we have compiled a list of 26 articles showing that there is an increasing number of studies reporting apparent elongation of telomeres (i.e., a net increase in TL from timet to timet+1) often in a considerable proportion of the individuals studied. Moreover, the few studies which have studied telomere elongation in detail show that increases in telomere length are unlikely to be due to measurement error alone. In this article, we argue that episodes of telomere elongation deserve more attention as they could reflect individual strategies to optimise life histories and maximise fitness, which may not be reflected in the overall telomere dynamics patterns. We propose that patterns of telomere (net) elongation may be partly determined by other factors than those causing telomere shortening, and therefore deserve analyses specifically targeted to investigate the occurrence of telomere elongation. We elaborate on two ecological hypotheses that have been proposed to explain patterns of telomere elongation (the 'excess resources elongation' and the 'last resort elongation' hypothesis) and we discuss the current evidence for (or against) these hypotheses and propose ways to test them. [ABSTRACT FROM AUTHOR]

In‐solution hybridisation enrichment of genetic variation is a valuable methodology in human paleogenomics. It allows enrichment of endogenous DNA by targeting genetic markers that are comparable between sequencing libraries. Many studies have used the 1240k reagent—which enriches 1,237,207 genome‐wide SNPs—since 2015, though access was restricted. In 2021, Twist Biosciences and Daicel Arbor Biosciences independently released commercial kits that enabled all researchers to perform enrichments for the same 1240 k SNPs. We used the Daicel Arbor Biosciences Prime Plus kit to enrich 132 ancient samples from three continents. We identified a systematic assay bias that increases genetic similarity between enriched samples and that cannot be explained by batch effects. We present the impact of the bias on population genetics inferences (e.g. Principal Components Analysis, ƒ‐statistics) and genetic relatedness (READ). We compare the Prime Plus bias to that previously reported of the legacy 1240k enrichment assay. In ƒ‐statistics, we find that all Prime‐Plus‐generated data exhibit artefactual excess shared drift, such that within‐continent relationships cannot be correctly determined. The bias is more subtle in READ, though interpretation of the results can still be misleading in specific contexts. We expect the bias may affect analyses we have not yet tested. Our observations support previously reported concerns for the integration of different data types in paleogenomics. We also caution that technological solutions to generate 1240k data necessitate a thorough validation process before their adoption in the paleogenomic community. [ABSTRACT FROM AUTHOR]

In this retrospective multicentre cohort study, we present the results of primary single-finger flexor tendon repairs in zones 1 to 3 between 2014 and 2021. Data from 218 patients were retrieved with their demographics, injury and surgery characteristics and therapy outcomes. The data were systematically collected and analysed at predefined time points up to 1 year after surgery. A good to excellent return of motion was achieved by 77% (Tang classification) and 92% (American Association for Surgery of the Hand classification) of patients at 1 year. The tendon rupture rate was 8.7%. Time had a significant impact on the recovery of finger motion and grip strength of up to 1 year, of patient satisfaction and upper extremity function up to 26 weeks, and of pain up to 13 weeks after surgery. Our results demonstrate that it is worthwhile to assess therapy outcomes over various measurement periods, as some outcomes may continue to improve up to 1 year after flexor tendon repair surgery. Level of evidence: III [ABSTRACT FROM AUTHOR]

Hydrogen sulfide is a toxic gas that disrupts numerous biological processes, including energy production in the mitochondria, yet fish in the Poecilia mexicana species complex have independently evolved sulfide tolerance several times. Despite clear evidence for convergence at the phenotypic level in these fishes, it is unclear if the repeated evolution of hydrogen sulfide tolerance is the result of similar genomic changes. To address this gap, we used a targeted capture approach to sequence genes associated with sulfide processes and toxicity from five sulfidic and five nonsulfidic populations in the species complex. By comparing sequence variation in candidate genes to a reference set, we identified similar population structure and differentiation, suggesting that patterns of variation in most genes associated with sulfide processes and toxicity are due to demographic history and not selection. But the presence of tree discordance for a subset of genes suggests that several loci are evolving divergently between ecotypes. We identified two differentiation outlier genes that are associated with sulfide detoxification in the mitochondria that have signatures of selection in all five sulfidic populations. Further investigation into these regions identified long, shared haplotypes among sulfidic populations. Together, these results reveal that selection on standing genetic variation in putatively adaptive genes may be driving phenotypic convergence in this species complex. [ABSTRACT FROM AUTHOR]

Foraging theory prescribes when optimal foragers should leave the current option for more rewarding alternatives. Actual foragers often exploit options longer than prescribed by the theory, but it is unclear how this foraging suboptimality arises. We investigated whether the upregulation of cholinergic, noradrenergic, and dopaminergic systems increases foraging optimality. In a double-blind, between-subject design, participants (N = 160) received placebo, the nicotinic acetylcholine receptor agonist nicotine, a noradrenaline reuptake inhibitor reboxetine, or a preferential dopamine reuptake inhibitor methylphenidate, and played the role of a farmer who collected milk from patches with different yield. Across all groups, participants on average overharvested. While methylphenidate had no effects on this bias, nicotine, and to some extent also reboxetine, significantly reduced deviation from foraging optimality, which resulted in better performance compared to placebo. Concurring with amplified goal-directedness and excluding heuristic explanations, nicotine independently also improved trial initiation and time perception. Our findings elucidate the neurochemical basis of behavioral flexibility and decision optimality and open unique perspectives on psychiatric disorders affecting these functions. [ABSTRACT FROM AUTHOR]

The tropical gar (Atractosteus tropicus) is the smallest member of the family Lepisosteidae; yet this species has a large socioeconomic impact in México and Central America where it is traditionally harvested commercially and for subsistence. While natural populations of tropical gar have been dwindling throughout its natural range, it is also an emergent aquaculture species that is produced in local hatcheries and grown out in privately owned ponds. The increased pressure on natural populations of A. tropicus and its increasing use in aquaculture production poses potential conflicts for the management and conservation of natural populations. Here, we investigated the population genetic structure of tropical gar populations, including over 200 individuals sampled in México, El Salvador, and Costa Rica. Using 11 microsatellite loci, we identified three genetic clusters with distinct geographic distributions, including a cluster in drainages along the Pacific versant of Central America, a cluster in the Grijalva and Usumacinta River basins that drain into the Gulf of México, and a cluster in the Río San Juan that drains into the Caribbean Sea. Given the degree of divergence observed, these results indicate the potential presence of evolutionary significant units within tropical gar that warrant separate fisheries and conservation management. We also found that tropical gar from an aquaculture facility along the Pacific versant of México were derived from Atlantic versant populations, indicating that individuals have already been translocated across biogeographic boundaries. We discuss how such translocations can negatively impact the natural population structure of tropical gar and provide recommendations for future research and aquaculture practices. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to assess outcomes in flexor pollicis longus tendon repairs with 6-strand core sutures with and without circumferential sutures. Methods: A 6-strand core suture technique with and without circumferential sutures was used. Thirty-three patients were summarized in the C group (circumferential group) and 16 patients in the NC group (non-circumferential group). After the surgery, the wrist was stabilized with a dorsal blocking splint and a controlled early active motion protocol was applied. At weeks 6, 13, and 26 data on demographics, type of injury, surgery, postoperative rehabilitation, complications such as re-rupture and the following outcome measurements were collected: range of motion and its recovery according to the Tang criteria, Kapandji score, thumb and hand strengths, Disabilities of the Arm, Shoulder and Hand score, and satisfaction. Results: There were no significant differences in range of motion and strength between the 2 treatment groups. In both groups, the outcome measurements increased over time and they expressed similar satisfaction with the surgical treatment. In 4 patients of the C group tendon repair ruptured and in 1 patient of the NC group. Conclusions: Six-strand repair technique is an effective procedure to assure early active motion after flexor pollicis longus tendon injuries and good results can also be achieved by omitting the circumferential suture. [ABSTRACT FROM AUTHOR]

Around the globe, the coronavirus pandemic has triggered various reactions of governments designed to contain the pandemic. Among other things, the pandemic led to an unforeseen and unprecedented closure of schools and daycare facilities. In turn, these closures might have forced parents to stay at home to care for their children who could not attend schools or kindergartens. From a social policy perspective, this raises the question of the extent to which parents' employment has been affected, as time spent on childcare might make parents reduce their working hours. To answer this question, we exploit within-country variations in school and childcare policies across the federal states of Germany to analyse their effect on parents' working time. In specific, we compare the working time of parents who live in different federal states with different restrictions regarding childcare in a difference-in-differences and difference-in-difference-in-differences framework. Our results reveal a non-negligible positive effect of an earlier and more far-reaching reopening of schools and daycare facilities on parents' employment. Our results indicate that prolonged closure goes along with negative employment effects for parents. Hence, containment and closure policies to prevent the spread of COVID-19 have substantial economic and social side effects. [ABSTRACT FROM AUTHOR]

Aldobionic acids are sugar acids which consist of a disaccharide with an anomeric acid group. The most famous is lactobionic acid (LBA). LBA is used in many applications such as food and beverages, pharmaceuticals and medicine, cosmetics or chemical processes. During the last decade, all these industries are observing a shift of consumer preferences towards plant-based options. Thus, the biotechnological industry is trying to replace the animal-derived LBA. Maltobionic acid (MBA) and cellobionic acid (CBA) are two stereoisomers of LBA which have emerged as vegan alternatives. However, MBA and CBA face different obstacles related to their industrial production. While traditionally used electrochemical or chemical catalysis often rely on cost intensive and/or hazardous catalysts, novel production methods with microorganisms are still poorly studied. In the first part, this paper discusses both alternatives in terms of their characteristics and applications. In the second part, it reviews the long-studied chemical production and the novel bioproduction methods, which are based on enzymatic and microbial systems. This review concludes with a discussion of future work needed to bring their production to the industrial scale. [ABSTRACT FROM AUTHOR]

Aims: In adults with congenital heart disease and systemic right ventricles, progressive right ventricular systolic dysfunction is common and is associated with adverse outcomes. Our aim was to assess the impact of the phosphodiesterase‐5‐inhibitor tadalafil on right ventricular systolic function. Methods and results: This was a double‐blind, randomized, placebo‐controlled, multicentre superiority trial (NCT03049540) involving 100 adults with systemic right ventricles (33 women, mean age: 40.7 ± 10.7 years), comparing tadalafil 20 mg once daily versus placebo (1:1 ratio). The primary endpoint was the change in right ventricular end‐systolic volume after 3 years of therapy. Secondary endpoints were changes in right ventricular ejection fraction, exercise capacity and N‐terminal pro‐B‐type natriuretic peptide concentration. Primary endpoint assessment by intention to treat analysis at 3 years of follow‐up was possible in 83 patients (42 patients in the tadalafil group and 41 patients in the placebo group). No significant changes over time in right ventricular end‐systolic volumes were observed in the tadalafil and the placebo group, and no significant differences between treatment groups (3.4 ml, 95% confidence interval −4.3 to 11.0, p = 0.39). No significant changes over time were observed for the pre‐specified secondary endpoints for the entire study population, without differences between the tadalafil and the placebo group. Conclusions: In this trial in adults with systemic right ventricles, right ventricular systolic function, exercise capacity and neuro‐hormonal activation remained stable over a 3‐year follow‐up period. No significant treatment effect of tadalafil was observed. Further research is needed to find effective treatment for improvement of ventricular function in adults with systemic right ventricles. [ABSTRACT FROM AUTHOR]

A growing body of research has placed the ventral striatum at the center of a network of cerebral regions involved in anticipating rewards in healthy controls. However, little is known about the functional connectivity of the ventral striatum associated with reward anticipation in healthy controls. In addition, few studies have investigated reward anticipation in healthy humans with different levels of schizotypy. Here, we investigated reward anticipation in eighty-four healthy individuals (44 females) recruited based on their schizotypy scores. Participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI.Participants showed the expected decrease in response times for highly rewarded trials compared to non-rewarded trials. Whole-brain activation analyses replicated previous results, including activity in the ventral and dorsal striatum. Whole-brain psycho-physiological interaction analyses of the left and right ventral striatum revealed increased connectivity during reward anticipation with widespread regions in frontal, parietal and occipital cortex as well as the cerebellum and midbrain. Finally, we found no association between schizotypal personality severity and neural activity and cortico-striatal functional connectivity. In line with the motivational, attentional, and motor functions of rewards, our data reveal multifaceted cortico-striatal networks taking part in reward anticipation in healthy individuals. The ventral striatum is connected to regions of the salience, attentional, motor and visual networks during reward anticipation and thereby in a position to orchestrate optimal goal-directed behavior. [ABSTRACT FROM AUTHOR]

Introduction: The influence of pain and a concomitant digital nerve injury on the course of rehabilitation after flexor tendon injury remains ambiguous. The objectives of the study were to: i) analyse the evolution of pain spanning one year after a primary flexor tendon repair in zones 1–3; ii) examine the differences in pain levels in patients with and without digital nerve injury; and iii) evaluate the relationship between pain, digital nerve injury and pain medication, total active motion (TAM), DASH scores and patient satisfaction. Methods: Data from 189 patients were retrieved from a flexor tendon registry between 2014 and 2020. Differences in pain, TAM, DASH and patient satisfaction were analysed. Multiple linear and binary logistic regression analyses were performed to determine the relationship between clinical outcomes. Results: Pain significantly decreased in the course of rehabilitation (p < 0.001 to 0.006). No relationship could be identified between nerve injury and pain (p = 0.21–0.97). In week 6, the presence of pain and a nerve injury were significantly associated with lower TAM scores (p = 0.001). In week 13, pain during motion (p < 0.001) and the presence of a nerve injury (p = 0.036) were significantly associated with worse DASH scores. Patient satisfaction was significantly inversely correlated to pain during motion in weeks 13 and 26 (p < 0.001). Conclusion: We found a significant relationship between pain during motion and pain medication intake, TAM, DASH scores and patient satisfaction. It is therefore advisable to closely monitor this parameter after flexor tendon injuries. Study registration: This multi-center cohort study is registered under https://clinicaltrials.gov: NCT04312412. [ABSTRACT FROM AUTHOR]

The evolutionarily recent dispersal of anatomically modern humans (AMH) out of Africa (OoA) and across Eurasia provides a unique opportunity to examine the impacts of genetic selection as humans adapted to multiple new environments. Analysis of ancient Eurasian genomic datasets (~1,000 to 45,000 y old) reveals signatures of strong selection, including at least 57 hard sweeps after the initial AMH movement OoA, which have been obscured in modern populations by extensive admixture during the Holocene. The spatiotemporal patterns of these hard sweeps provide a means to reconstruct early AMH population dispersals OoA. We identify a previously unsuspected extended period of genetic adaptation lasting ~30,000 y, potentially in the Arabian Peninsula area, prior to a major Neandertal genetic introgression and subsequent rapid dispersal across Eurasia as far as Australia. Consistent functional targets of selection initiated during this period, which we term the Arabian Standstill, include loci involved in the regulation of fat storage, neural development, skin physiology, and cilia function. Similar adaptive signatures are also evident in introgressed archaic hominin loci and modern Arctic human groups, and we suggest that this signal represents selection for cold adaptation. Surprisingly, many of the candidate selected loci across these groups appear to directly interact and coordinately regulate biological processes, with a number associated with major modern diseases including the ciliopathies, metabolic syndrome, and neurodegenerative disorders. This expands the potential for ancestral human adaptation to directly impact modern diseases, providing a platform for evolutionary medicine. [ABSTRACT FROM AUTHOR]

Methotrexate is an immunosuppressant and chemotherapeutic agent used in the treatment of a range of autoimmune disorders and cancers. Its main serious adverse effects, bone marrow suppression and gastrointestinal complications, arise from its antimetabolite effect. Nevertheless, hepatotoxicity and nephrotoxicity are two widely described adverse effects of methotrexate. Its hepatotoxicity has been studied mainly in the low-dose, chronic setting, where patients are at risk of fibrosis/cirrhosis. Studies of acute hepatoxicity of high dose methotrexate, such as during chemotherapy, are scarce. We present the case of a 14-year-old patient who received high-dose methotrexate and subsequently developed acute fulminant liver failure and acute kidney injury. Genotyping of MTHFR (Methylene tetrahydrofolate reductase gene), ABCB1 (codes for P-glycoprotein, intestinal transport and biliary excretion), ABCG2 (codes for BCRP, intestinal transporter and renal excretion) and SLCO1B1 (codes for OATP1B1, hepatic transporter) identified variants in all the genes analysed that predicted a reduced rate of methotrexate elimination and thus may have contributed to the clinical situation of the patient. Precision medicine involving pharmacogenomic testing could potentially avoid such adverse drug effects. [ABSTRACT FROM AUTHOR]