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Abstract Background Skeletal dysplasia encompasses a heterogeneous group of genetic disorders characterized by an abnormal development of bones, joints, and cartilage. Two Chianina half‐sibling calves from consanguineous mating with congenital skeletal malformations and cardiac abnormalities were identified. Hypothesis/Objectives To characterize the disease phenotype, to evaluate its genetic cause, and to determine the prevalence of the deleterious alleles in the Chianina population. Animals Two affected calves, their parents and 332 Chianina bulls. Methods The affected animals underwent clinicopathological investigation. Whole‐genome sequencing trio‐approach and PCR‐based assessment of the frequency of TDP‐glucose 4,6‐dehydratase (TGDS) and laminin subunit alpha 4 (LAMA4) alleles were performed. Results The cases presented with retarded growth, poor nutritional status associated with muscular atrophy and angular deformities of the hindlimbs. Radiologic examination identified generalized osteopenia and shortening of the limb long bones. Necropsy showed osteochondrodysplastic limbs and dilatation of the heart right ventricle. On histological examination, the physeal cartilages were characterized by multifocal mild to moderate loss of the normal columnar arrangement of chondrocytes. Osteopenia also was observed. Genetic analysis identified a missense variant in TGDS and a splice‐site variant in LAMA4, both of which were homozygous in the 2 cases. Parents were heterozygous and allele frequency in the Chianina population for the TGDS variant was 5% and for the LAMA4 variant was 2%. Conclusions and Clinical Importance Genetic findings identified 2 potentially pathogenic alleles in TGDS and LAMA4, but no clear mode of inheritance could be determined.

Abstract Aims The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics. Methods and results Patients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low‐dose loop diuretic and high‐dose loop diuretic. Primary outcome was 5 year all‐cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25 mg, and accordingly patients were divided in no/low dose (i.e. ≤25 mg, n = 257, 65%) vs. high dose (i.e. >25 mg, n = 140, 35%). Patients in the high‐dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5 year survival was significantly shorter in patients in the high‐dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome. Conclusions Use of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor.

Abstract The new key biodiversity areas (KBA) standard is an important method for identifying regions of the planet‐hosting unique biodiversity. KBAs are identified through the implementation of threshold‐based criteria that can be applied to any target species and region. Current methods to rapidly assess the existence of potential KBAs in different areas of the planet still present important challenges, although they are needed to accelerate the KBA identification process for large numbers of species globally. We developed a methodology to scan geographical regions and detect potential KBAs under multiple criteria. We tested the methodology on 59 species of reptiles and amphibians in Italy through the application of selected KBA criteria. Potential KBAs were identified for multiple species under most criteria, covering 1.4%–12% of the study area, depending on analytical settings. Cell size used to identify KBAs played an important role in shaping the distribution of potential KBAs, also affecting the overlap between areas triggered by different criteria. New potential KBAs identified in this study are only partially coincident with current KBAs in Italy (previously identified for birds) and within the national protected areas.

Abstract Objectives Mandatory newborn screening (NBS) for spinal muscular atrophy (SMA) was implemented for the first time in Italy at the end of 2021, allowing the identification and treatment of patients at an asymptomatic stage. Methods DNA samples extracted from dried blood spot (DBS) from newborns in Apulia region were analysed for SMA screening by using a real‐time PCR‐based assay. Infants harbouring homozygous deletion of SMN1 exon 7 confirmed by diagnostic molecular tests underwent clinical and neurophysiological assessment and received a timely treatment. Results Over the first 20 months since regional NBS introduction, four out of 42,492 (0.009%) screened children were found to carry a homozygous deletion in the exon 7 of SMN1 gene, with an annual incidence of 1:10,623. No false negatives were present. Median age at diagnosis was 7 days and median age at treatment was 20.5 days. Three of them had two copies of SMN2 and received gene therapy, while the one with three SMN2 copies was treated with nusinersen. All but one were asymptomatic at birth, showed no clinical signs of disease after a maximum follow‐up of 16 months and reached motor milestones appropriate with their age. The minimum interval between diagnosis and the treatment initiation was 9 days. Interpretation The timely administration of disease‐modifying therapies prevented presymptomatic subjects to develop disease symptoms. Mandatory NBS for SMA should be implemented on a national scale.

Abstract Background Sleep disorders are often complained by cancer patients and can last years after the end of therapies, leading to different negative consequences. Non‐pharmacological strategies such as exercise interventions may be considered to counteract this phenomenon. The literature supports the beneficial effects of aerobic training (AT), while evidence on resistance training (RT) is scarce. Accordingly, our systematic review aims to investigate the potential novel effect of RT on sleep outcomes in cancer survivors. Methods The literature search was conducted on MEDLINE (Pubmed), Web of Science, Scopus, and Cochrane Central Register of Controlled Trials databases, including only randomized controlled trials (RCTs). The screening procedure was conducted using the web‐based software COVIDENCE. Sleep outcomes assessed through self‐reported questionnaires or objective sleep measurements were extracted from RCTs recruiting cancer survivors of any age and gender, on or off treatment. The risk of bias (RoB) for each study was assessed using the Cochrane RoB 2 tool for RCTs. Meta‐analytic syntheses were performed on sleep quality and insomnia. Results A total of 21 studies were included in the review. Considering the mean percentage differences of all studies combined, promising positive results were found after combined aerobic and resistance exercise program (COMB) for sleep quality (−19%) and sleep disturbance (−17.3%). The meta‐analysis results showed significant improvement for both sleep quality and insomnia (d = 0.28, SE: 0.11, Z = 2.51, p

Abstract Febrile infection‐related epilepsy syndrome (FIRES) is a prolonged refractory status epilepticus (SE) that develops among healthy individuals after a febrile infection. FIRES treatment is challenging due to its poor response to antiseizure medications (ASMs) and anesthetic drugs. The use of cannabidiol (CBD) as an adjunctive treatment has been suggested, albeit data about its role in the acute phase is lacking. This report describes the use of purified CBD in the acute phase of two pediatric cases of FIRES and their long‐term outcome. Both children were treated with several ASMs, immunomodulators, anesthetics, and nonpharmacological treatment (ketogenic diet). CBD was administered, as an adjunctive treatment, through nasogastric tube about 30 days after onset. SE resolved within 3 days of reaching the target dose and both were seizure‐free for 1 year after. Although it is difficult to define the extent to which each previous therapy contributed to recovery, in both cases CBD therapy was a turning point, reinforcing its potential role as add‐on treatment in the acute phase of FIRES.

Abstract Experimental introductions of species have provided some of the most tractable examples of rapid phenotypic changes, which may reflect plasticity, the impact of stochastic processes, or the action of natural selection. Yet to date, very few studies have investigated the neutral and potentially adaptive genetic impacts of experimental introductions. We dissect the role of these processes in shaping the population differentiation of wall lizards in three Croatian islands (Sušac, Pod Kopište, and Pod Mrčaru), including the islet of Pod Mrčaru, where experimentally introduced lizards underwent rapid (~30 generations) phenotypic changes associated with a shift from an insectivorous to a plant‐based diet. Using a genomic approach (~82,000 ddRAD loci), we confirmed a founder effect during introduction and very low neutral genetic differentiation between the introduced population and its source. However, genetic depletion did not prevent rapid population growth, as the introduced lizards exhibited population genetic signals of expansion and are known to have reached a high density. Our genome‐scan analysis identified just a handful of loci showing large allelic shifts between ecologically divergent populations. This low overall signal of selection suggests that the extreme phenotypic differences observed among populations are determined by a small number of large‐effect loci and/or that phenotypic plasticity plays a major role in phenotypic changes. Nonetheless, functional annotation of the outlier loci revealed some candidate genes relevant to diet‐induced adaptation, in agreement with the hypothesis of directional selection. Our study provides important insights on the evolutionary potential of bottlenecked populations in response to new selective pressures on short ecological timescales.

Abstract Due to global climate change, heat stress is increasingly harming the growth, development, overall biomass, and grain yield of numerous crops. Heat stress impairs pollen development and thus reduces seed set in Sorghum bicolor (L.) Moench; however, the effects of heat stress on anther development at specific stages and tiller formation remain incompletely understood. Here we report that exposure to heat stress [42°C/32°C (day/night)] at pollen mother cell (PMC) and booting stages profoundly disrupts tapetum and pollen development, resulting in a significant decrease in grain yield in sorghum. Sorghum plants subjected to 9 days or less of heat stress at the PMC stage exhibited normal pollen viability, but 12 days of heat stress caused almost complete loss of grain yield and the formation of nonviable pollen grains. Similarly, sorghum plants that were heat‐stressed for 3 days at the booting stage produced few seeds. Further analysis revealed that aberrant tapetum and pollen development contributed to the sterility of pollen in these heat‐stressed plants. Notably, in addition to inhibiting plant height, a 12‐day heat stress at the PMC stage promoted the formation of basal tillers, whereas a 3‐day heat stress at the booting stage stimulated the formation of apical tillers, which helped salvage seed yield under heat stress conditions. Moreover, the application of exogenous auxin promoted the formation of apical tillers and leaf numbers per apical tiller. Collectively, our findings suggest that sorghum is susceptible to heat stress during both early and late anther development, and auxin might be involved in governing the formation of apical tillers.

Abstract Objectives Intravenous thrombolysis (IVT) and endovascular therapy (EVT) are the mainstays of treatment for large vessel occlusion stroke (LVOS). Prior studies have examined why patients have not received IVT, the most cited reasons being last‐known‐well (LKW) to hospital arrival of >4.5 hours and minor/resolving stroke symptoms. Given that LVOS patients typically present moderate‐to‐severe neurologic deficits, these patients should be easier to identify and treat than patients with minor strokes. This investigation explores why IVT was not administered to a cohort of LVOS patients who underwent EVT. Methods This is an analysis of the Optimizing the Use of Prehospital Stroke Systems of Care (OPUS‐REACH) registry, which contains patients from 9 endovascular centers who underwent EVT between 2015 and 2020. The exposure of interest was the receipt of intravenous thrombolysis. Descriptive summary statistics are presented as means and SDs for continuous variables and as frequencies with percentages for categorical variables. Two‐sample t tests were used to compare continuous variables and the chi‐square test was used to compare categorical variables between those who received IVT and those who did not receive EVT. Results Two thousand forty‐three patients were included and 60% did not receive IVT. The most common reason for withholding IVT was LKW to arrival of >4.5 (57.2%). The second most common contraindication was oral anticoagulation (15.5%). On multivariable analysis, 2 factors were associated with not receiving IVT: increasing age (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.78–0.93) and increasing time from LKW‐to hospital arrival (OR 0.45 95% CI 0.46–0.49). Conclusion Like prior studies, the most frequent reason for exclusion from IVT was a LKW to hospital presentation of >4.5 hours; the second reason was anticoagulation. Efforts must be made to increase awareness of the time‐sensitive nature of IVT and evaluate the safety of IVT in patients on oral anticoagulants.

Abstract The problem of global amphibian declines has prompted extensive research over the last three decades. Initially, the focus was on identifying and characterizing the extent of the problem, but more recently efforts have shifted to evidence‐based research designed to identify best solutions and to improve conservation outcomes. Despite extensive accumulation of knowledge on amphibian declines, there remain knowledge gaps and disconnects between science and action that hamper our ability to advance conservation efforts. Using input from participants at the ninth World Congress of Herpetology, a U.S. Geological Survey Powell Center symposium, amphibian on‐line forums for discussion, the International Union for Conservation of Nature Assisted Reproductive Technologies and Gamete Biobanking group, and respondents to a survey, we developed a list of 25 priority research questions for amphibian conservation at this stage of the Anthropocene. We identified amphibian conservation research priorities while accounting for expected tradeoffs in geographic scope, costs, and the taxonomic breadth of research needs. We aimed to solicit views from individuals rather than organizations while acknowledging inequities in participation. Emerging research priorities (i.e., those under‐represented in recently published amphibian conservation literature) were identified, and included the effects of climate change, community‐level (rather than single species‐level) drivers of declines, methodological improvements for research and monitoring, genomics, and effects of land‐use change. Improved inclusion of under‐represented members of the amphibian conservation community was also identified as a priority. These research needs represent critical knowledge gaps for amphibian conservation although filling these gaps may not be necessary for many conservation actions.

Abstract Objective To compare serum levels of the astrocyte biomarker glial fibrillary acidic protein (GFAP) in patients with amyotrophic lateral sclerosis (ALS) and neurologically healthy controls and to analyze the relations between serum GFAP (sGFAP) and phenotype in ALS. Methods We studied 114 ALS patients and 38 controls. sGFAP was quantified with single molecule array (Simoa) technology. Results In both ALS patients and controls, sGFAP moderately correlated with age. ALS patients had higher sGFAP levels compared to controls, but this yielded a weak discriminative performance (AUC = 0.6198). In ALS, sGFAP was not associated with most of the motor phenotypic features, including site of onset, functional status, disease progression rate, disease stage, and indices of upper (UMN) and lower motor neuron (LMN) impairment. However, sGFAP negatively correlated with cognitive scores regarding ALS‐nonspecific functions, particularly memory (r = −0.2082) and tended to be higher in ALS patients with eye movement abnormalities (p = 0.0628). sGFAP also correlated with polysomnographic indices of oxygen desaturation (ODI; r = 0.2639) and apnea‐hypopnea (AHI; r = 0.2858). In a multivariate analysis, sGFAP was negatively associated with survival (HR = 1.005). Relevantly, we found a negative correlation between sGFAP and estimated glomerular filtration rate (eGFR; r = −0.3500). Interpretation Our work provides neurochemical evidence of astrocyte involvement in ALS pathophysiology and particularly in the development of extra‐motor manifestations (namely, cognitive – memory – impairment) and respiratory dysfunction. The negative correlation between sGFAP and eGFR has practical relevance and should not be disregarded in future investigations.

Background Intravenous thrombolysis (IVT) and endovascular therapy (EVT) are both important treatments for large‐vessel occlusion stroke. However, it is still unclear how the timing of IVT, EVT, and the need for transfer of a patient to an endovascular stroke center for EVT affect outcomes. In this investigation, we study the interaction between IVT, rapidity to EVT, and need for transfer among patients with large‐vessel occlusion stroke. Methods This investigation is an analysis of the OPUS‐REACH (Optimizing the Use Prehospital Stroke Systems of Care–Reacting to Changing Paradigms) registry of patients with large‐vessel occlusion stroke from 9 endovascular centers in the United States. Using the database, we extracted baseline characteristics of patients, whether the patient received IVT, and time intervals in the patients’ care. Patient demographics and characteristics were compared between 2 groups using the χ2 test for categorical variables and 2‐sample t‐tests or Wilcoxon rank‐sum tests for continuous variables. Multivariable logistic regression was performed to determine the adjusted associations of the variables with 90‐day dichotomized modified Rankin Scale outcome. Results A total of 1171 patients were included in the final analysis, and 38.9% had good functional outcome at 90 days. Male sex and lower initial National Institutes of Health Stroke Scale score were nonmodifiable factors associated with good clinical outcomes. We saw no differences in outcome whether a patient underwent primary or secondary transport. On multiple variable analysis, the receipt of IVT was the only modifiable factor associated with good outcomes. We found no overall effect of time from last known well to EVT on 90‐day outcomes unless the patient received IVT. Conclusions In this investigation, receipt of IVT was independently associated with improved outcomes at 90 days with an odds ratio of 1.51. Neither shorter time from last known well to EVT nor direct transport to an endovascular stroke center versus transfer to an endovascular stroke center was associated with improved outcomes. We therefore conclude that prehospital algorithms must account for the timely administration of IVT over time to EVT.

Abstract Aims To define plasma concentrations, determinants, and optimal prognostic cut‐offs of soluble suppression of tumorigenesis‐2 (sST2), high‐sensitivity cardiac troponin T (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in women and men with chronic heart failure (HF). Methods and results Individual data of patients from the Biomarkers In Heart Failure Outpatient Study (BIOS) Consortium with sST2, hs‐cTnT, and NT‐proBNP measured were analysed. The primary endpoint was a composite of 1 year cardiovascular death and HF hospitalization. The secondary endpoints were 5 year cardiovascular and all‐cause death. The cohort included 4540 patients (age 67 ± 12 years, left ventricular ejection fraction 33 ± 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/mL, P

Background Once the return of spontaneous circulation after out‐of‐hospital cardiac arrest is achieved, a 12‐lead ECG is strongly recommended to identify candidates for urgent coronary angiography. ECG has no apparent role in mortality risk stratification. We aimed to assess whether ECG features could be associated with 30‐day survival in patients with out‐of‐hospital cardiac arrest. Methods and Results All the post‐return of spontaneous circulation ECGs from January 2015 to December 2018 in 3 European centers (Pavia, Lugano, and Vienna) were collected. Prehospital data were collected according to the Utstein style. A total of 370 ECGs were collected: 287 men (77.6%) with a median age of 62 years (interquartile range, 53–70 years). After correction for the return of spontaneous circulation‐to‐ECG time, age >62 years (hazard ratio [HR], 1.78 [95% CI, 1.21–2.61]; P=0.003), female sex (HR, 1.5 [95% CI, 1.05–2.13]; P=0.025), QRS wider than 120 ms (HR, 1.64 [95% CI, 1.43–1.87]; P1 segment (HR, 1.75 [95% CI, 1.59–1.93]; P

Background Access to endovascular stroke centers (ESCs) is crucial for patients to receive optimal care for large‐vessel occlusion strokes. Disparities in stroke care are well documented, including differences in patients who receive intravenous thrombolysis and endovascular therapy. Here, we describe racial, ethnic, sex, and social disparities in access to ESCs using the Social Vulnerability Index (SVI), a composite measure of a community's health. Methods This is a population‐based study of 4 Northeastern states. We geocoded all ESCs in New York, New Jersey, Pennsylvania, and Delaware and calculated the distance from the centroid of each census tract to the nearest ESC. We then used the US Centers for Disease Control's Social Vulnerability Index and its 4 subcomponents to calculate the health of that census tract. Results are presented as mean drive times by quartile of SVI (quartile 1=least vulnerable, quartile 4=most vulnerable) and the mean SVI dichotomized to census tracts located less than and greater than 60 minutes to the nearest ESC. Results A total of 42 000 000 people and 10 000 census tracts were included in our data. There were no significant differences in the mean SVI for census with drive times of 60 minutes to the nearest ESC. However, there were significant differences in 2 subcomponents of the SVI: Minority Status & Language and Household Composition & Disability. In the Minority Status subcomponent of the SVI, those in the most vulnerable census tracts (quartile 4) were located closest to ESCs compared with the least vulnerable census tracts (quartile 1), while for the Household Composition subcomponent, the most vulnerable census tracts were located farthest from the ESCs. Conclusion The SVI is a valuable tool for assessing disparities in access to advanced stroke care and predicting where additional ESCs should be added to benefit the population as a whole.

Abstract Aims The angiotensin receptor–neprilysin inhibitor (ARNI), sacubitril/valsartan, has been shown to be effective in treatment of patients with heart failure (HF), but limited data are available in patients with advanced disease. This retrospective observational study assessed the effects of ARNI treatment in patients with advanced HF. Methods and results We reviewed medical records of all advanced HF patients evaluated at our centre for unconventional therapies from September 2016 to January 2019. We studied 44 patients who started ARNI therapy and who had a haemodynamic assessment before beginning ARNI and after 6 ± 2 months. The primary endpoint was variation in pulmonary pressures and filling pressures at 6 months after starting ARNI therapy. Mean patient age was 51.6 ± 7.4 years; 84% were male. At 6 ± 2 months after starting ARNI, there was significant reduction of systolic pulmonary artery pressure [32 mmHg, interquartile range (IQR) 27–45 vs. 25 mmHg, IQR 22.3–36.5; P

Abstract Hemifacial microsomia (HFM) was diagnosed in a 9‐day‐old Romagnola calf. The condition was characterized by microtia of the left ear, anotia of the right ear, asymmetry of the face, and deafness. Magnetic resonance imaging revealed agenesis of the right pinna and both tympanic bullae, asymmetry of the temporal bones and temporomandibular joints, and right pontine meningocele. Brainstem auditory evoked responses confirmed the impaired auditory capacity. At gross post mortem examination, there was agenesis and hypoplasia of the right and the left external ear, respectively. No histological abnormalities were detected in the inner ears. A trio whole‐genome sequencing approach was carried out and identified a private homozygous missense variant in LAMB1 affecting a conserved residue (p.Arg668Cys). Genotyping of 221 Romagnola bulls revealed a carrier prevalence

Abstract There has been a steady rise in the use of dormant propagules to study biotic responses to environmental change over time. This is particularly important for organisms that strongly mediate ecosystem processes, as changes in their traits over time can provide a unique snapshot into the structure and function of ecosystems from decades to millennia in the past. Understanding sources of bias and variation is a challenge in the field of resurrection ecology, including those that arise because often‐used measurements like seed germination success are imperfect indicators of propagule viability. Using a Bayesian statistical framework, we evaluated sources of variability and tested for zero‐inflation and overdispersion in data from 13 germination trials of soil‐stored seeds of Schoenoplectus americanus, an ecosystem engineer in coastal salt marshes in the Chesapeake Bay. We hypothesized that these two model structures align with an ecological understanding of dormancy and revival: zero‐inflation could arise due to failed germinations resulting from inviability or failed attempts to break dormancy, and overdispersion could arise by failing to measure important seed traits. A model that accounted for overdispersion, but not zero‐inflation, was the best fit to our data. Tetrazolium viability tests corroborated this result: most seeds that failed to germinate did so because they were inviable, not because experimental methods failed to break their dormancy. Seed viability declined exponentially with seed age and was mediated by seed provenance and experimental conditions. Our results provide a framework for accounting for and explaining variability when estimating propagule viability from soil‐stored natural archives which is a key aspect of using dormant propagules in eco‐evolutionary studies.

Abstract Background Patients in heart transplantation (HTx) waiting list for advanced heart failure (HF) are susceptible to acute deterioration refractory to standard HF medical therapies. Limited data are available on long‐term in‐hospital continuous intravenous (IV) inotropic therapy as bridge to definite therapies. Methods and results We reviewed medical records of all heart transplant recipients treated in the pre‐HTx phase with in‐hospital continuous IV inotropes at our institution between 2012 and 2018. We analysed data before the beginning of continuous IV therapy and at the moment of HTx. We report data of 24 patients (mean age of 43.5 ± 15.7 years) treated with IV inotropes as bridge to HTx (median follow‐up of 28 months after HTx). The main length of IV inotropic therapy was 84 ± 66 days (min 22; max 264 days). At the beginning, the most frequently used inotrope was dopamine (median dosage of 3 mcg/kg/min, interquartile range 2.5–3.75), alone (n = 11, 46%) or in combination with other inotropes (n = 13, 54%). In 18 patients, the class of inotropes was changed during the hospitalization. We registered a progressive improvement of perfusion markers and neuro‐hormonal activation. Conclusion In‐hospital continuous parenteral inotropic therapy may serve as a temporary pharmacological bridge to HTx in patients with advanced HF that are actively listed to HTx with good reply in terms of prognosis and perfusion markers.

Abstract Assessing biodiversity loss and species extinction is necessary to warn society and raise awareness of the impacts of ongoing climate change. Prioritizing protected areas is the pragmatic and applicable management measure under the pressure of ongoing climate change and limited resources to conserve species at risk of extinction. We developed a novel conservation index (CI) to prioritize areas and populations of an endangered mountain tree species that need protection in the face of ongoing climate change, as conservation of all populations may not be realistic. This CI integrates (1) mountain topography to identify potential refugial areas with suitable microclimates, (2) genetic diversity to assess the adaptive capacity of local populations, and (3) hypothetical climate change in the species' range. We applied this CI to Atlas cedar, an endemic and threatened species whose populations are scattered throughout the Moroccan mountains. This index provided a scale for 33 populations studied and suggests that genetically diverse populations located in rugged areas where future local climate may overlap with their current climatic niche should receive a higher conservation priority. This index may also be applicable to other mountain species with scattered populations and is likely to be more accurate if more precise climate data are used at the microrefugia scale.

Abstract Objective To assess the dynamics of “pseudo‐atrophy,” the accelerated brain volume loss observed after initiation of anti‐inflammatory therapies, in patients with multiple sclerosis (MS). Methods Monthly magnetic resonance imaging (MRI) data of patients from the IMPROVE clinical study (NCT00441103) comparing relapsing‐remitting MS patients treated with interferon beta‐1a (IFNβ‐1a) for 40 weeks versus those receiving placebo (16 weeks) and then IFNβ‐1a (24 weeks) were used to assess percentage of gray (PGMVC) and white matter (PWMVC) volume changes. Comparisons of PGMVC and PWMVC slopes were performed with a mixed effect linear model. In the IFNβ‐1a‐treated arm, a quadratic term was included in the model to evaluate the plateauing effect over 40 weeks. Results Up to week 16, PGMVC was −0.14% per month in the placebo and −0.27% per month in treated patients (P

Abstract We think that thalassemia is not necessarily a cause of aggravation of the clinical course in COVID‐19; however, certain key factors must be considered, such as the anemic condition, the likely pathogenic role of the virus on hemoglobin, and the hypercoagulable state to prevent any complications.

Background Central apneas (CA) are a frequent comorbidity in patients with heart failure (HF) and are associated with worse prognosis. The clinical and prognostic relevance of CA in each sex is unknown. Methods and Results Consecutive outpatients with HF with either reduced or mildly reduced left ventricular ejection fraction (n=550, age 65±12 years, left ventricular ejection fraction 32%±9%, 21% women) underwent a 24‐hour ambulatory polygraphy to evaluate CA burden and were followed up for the composite end point of cardiac death, appropriate implantable cardioverter‐defibrillator shock, or first HF hospitalization. Compared with men, women were younger, had higher left ventricular ejection fraction, had lower prevalence of ischemic etiology and of atrial fibrillation, and showed lower apnea‐hypopnea index (expressed as median [interquartile range]) at daytime (3 [0–9] versus 10 [3–20] events/hour) and nighttime (10 [3–21] versus 23 [11–36] events/hour) (all P0.05), also after matching women and men for possible confounders. Conclusions In chronic HF, CA are associated with a greater risk of adverse events in women than in men.

Abstract Limited information is available on the efficacy of front‐line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real‐world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty‐seven patients with creatinine clearance (CrCl) 6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression‐free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patients ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02‐1.10, P

Abstract The worldwide biodiversity crisis with the resulting need to increase species protection has led researchers to pursue and select survey methods that guarantee the best quality of data and produce the least negative effects on wild animals. Plethodontids are the most diverse family of salamanders; all species are very sensitive to human handling and noninvasive, but accurate, measurement methods are needed to reduce researchers’ impact. Here, we tested the reliability of a noninvasive post hoc method in estimating the snout–vent length (SVL) from photographs showing salamanders’ dorsal view. The correlation between the estimated snout–vent length (SVLe) and the conventional SVL was high (R2m = .81), and no significant difference occurred between operators with different experience. Finally, we list the numerous advantages for the use of SVLe in terms of data quality and in reducing the stress caused to wild animals.

Abstract Background Chianina, Romagnola, and Marchigiana are the 3 most important Italian breeds of cattle raised in the Apennine Mountains. Inherited disorders have been reported in the Chianina and Romagnola breeds but not in the Marchigiana breed. Recently, a case resembling recessively inherited KDM2B‐associated paunch calf syndrome (PCS) in Romagnola cattle was identified in Marchigiana cattle. Hypothesis/Objectives To characterize the features of the observed congenital anomaly, evaluate its possible genetic etiology, and determine the prevalence of the deleterious allele in the Marchigiana population. Animals A single stillborn Marchigiana calf was referred for clinicopathological examination because of the presence of PCS‐like morphological lesions. Methods The animal was necropsied and the calf and its parents were genotyped. A PCR‐based direct gene test was applied to determine the KDM2B genotype and 114 Marchigiana bulls were genotyped. Results The pathological phenotype included facial deformities, enlarged fluid‐filled abdomen, and hepatic fibrosis. The affected animal was the offspring of consanguineous mating and homozygous presence of the KDM2B missense variant was confirmed. Both parents were heterozygous for KDM2B and the prevalence of carriers in a selected population of Marchigiana bulls was

Abstract Sedimentary ancient DNA (SedaDNA) is an emerging tool to reconstruct past biodiversity with high taxonomic resolution. Its growing popularity has stimulated an increasing complexity of SedaDNA data production (e.g., DNA extraction, amplification, and sequencing; authentication of molecules; bioinformatics). Conversely, less attention has been devoted to how appropriate statistical analyses can help to extract ecological information from SedaDNA. Until now, ecological studies based on SedaDNA have taken limited advantage of the multiple statistical and numerical methods available for analysis. Here, we present a range of numerical approaches that can be particularly useful to multispecies ecological analysis on SedaDNA, with a special focus on biodiversity studies on macroorganisms. We discuss the advantages and complexity of such methods and describe how some of them can be optimized for ecological analyses of SedaDNA‐based metabarcoding data, with a special focus on SedaDNA studies. First, site occupancy‐detection models can help to better ascertain the variation through time of the occurrence of target species and to identify the factors determining their detection through time. Second, several approaches can be used to estimate variation of relative abundance. Even though methods for abundance estimation have major limitations, they can provide useful information on temporal variation of ecosystem functions. Third, approaches exist to obtain better measures of species diversity, while taking into account the uncertainties of species abundance and identification. Fourth, techniques of clustering, ordination, and constrained ordination allow identification of temporal trends and testing of candidate drivers of community variation. Finally, structural equation models can be used to assess complex causal relationships among biodiversity, human activities, and environment. SedaDNA studies can make use of a broad panel of analytical approaches, which can improve our understanding of long‐term biodiversity changes, maximizing the information we can obtain from past ecosystems.

Abstract Necrotizing Sweet syndrome is a recently described entity that can pose significant challenges for management. Although necrotizing fasciitis can be rapidly fatal in the absence of prompt surgical management, necrotizing Sweet syndrome may actually be worsened by any surgical intervention. Authors want to emphasize and increase awareness of this rare presentation.