Impact of Holocene environmental change on the evolutionary ecology of an Arctic top predator.

The Arctic is among the most climatically sensitive environments on Earth, and the disappearance of multiyear sea ice in the Arctic Ocean is predicted within decades. As apex predators, polar bears are sentinel species for addressing the impact of environmental variability on Arctic marine ecosystems. By integrating genomics, isotopic analysis, morphometrics, and ecological modeling, we investigate how Holocene environmental changes affected polar bears around Greenland. We uncover reductions in effective population size coinciding with increases in annual mean sea surface temperature, reduction in sea ice cover, declines in suitable habitat, and shifts in suitable habitat northward. Furthermore, we show that west and east Greenlandic polar bears are morphologically, and ecologically distinct, putatively driven by regional biotic and genetic differences. Together, we provide insights into the vulnerability of polar bears to environmental change and how the Arctic marine ecosystem plays a vital role in shaping the evolutionary and ecological trajectories of its inhabitants.

Increased histological severity and chronicity of interface inflammation in anti-MDA5 dermatomyositis-A comparative dermatopathological analysis.

Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis is characterized by serological detection of anti-MDA5 antibody and rapidly progressive interstitial lung disease. In this study, the largest cohort of skin biopsies to date of anti-MDA5 dermatomyositis was reviewed and compared with cases of dermatomyositis with negative serology. Findings contribute to the histological diagnosis and evaluation of the severity of cutaneous inflammation in anti-MDA5 dermatomyositis. Skin biopsies collected over a 7-year period from individuals with clinically and histologically confirmed dermatomyositis with anti-MDA5 serology were reviewed. A total of 46 cases with 17 anti-MDA5 positive cases were retrieved. Patients with positive antibody were younger (53.7 vs. 60.6 years, p = .013). No differences in epidermal changes (p > .05) were observed. Pertaining to interface changes, anti-MDA5 dermatomyositis showed a higher degree of pigmentary incontinence (p = .014), suggesting increased and sustained cutaneous inflammation. Periodic acid-Schiff (PAS) stain demonstrated a greater degree of basement membrane thickening (p = .045). Other parameters, including dermal inflammation, dermal mucin deposition and vasculitic/vasculopathic features did not show statistical difference between anti-MDA5 positive and negative dermatomyositis (p > .05). Findings suggest increased cutaneous inflammation for anti-MDA5 dermatomyositis. In skin biopsies, marked pigmentary incontinence or basement membrane thickening should raise suspicion of anti-MDA5 dermatomyositis.

When big data initiatives meet: Data sharing between THANADOS and IsoArcH for early medieval cemeteries in Austria.

This paper reports carbon, nitrogen, and sulfur stable isotope data obtained from bone collagen of humans from the early medieval cemeteries of Hemmaberg/Gora svete Heme and Oberleiserberg located in Austria. The Hemmaberg/Gora svete Heme cemetery, dating from the 8th to the 11th century, comprises 29 graves, from which 15 individuals were analyzed. The Oberleiserberg cemetery, established in the first half of the 11th century, includes 71 graves as well as several incidental finds of human bones, from which 75 samples were analyzed. Both cemeteries show comparable δ13C data (mean for Oberleiserberg: -17.5 ± 1.2 ‰, 1σ; mean for Hemmaberg: -16.4 ± 1.6‰, 1σ). However, the δ15N values of individuals from Oberleiserberg (mean: +10.4 ± 1.5‰, 1σ) are slightly higher than those of individuals from Hemmaberg/Gora svete Heme (mean: +8.8 ± 1.1‰,1σ). The δ34S values were only obtained on the individuals from Oberleiserberg, and show a mean value of -0.9 ± 2.0 ‰ (1σ). Beyond the isotopic data presented in this article, we lay the foundations for cooperation between the IsoArcH database (https://isoarch.eu) [1] and the THANADOS (https://thanados.net) [2] project. While IsoArcH primarily stores isotope-related datasets for bioarchaeology, THANADOS stores data on archaeologically and anthropologically researched burials. Moving forward, IsoArcH and THANADOS plan to work closely together to integrate their databases. This collaboration presents a promising opportunity for both projects to pool their resources and knowledge, offering a wealth of information for researchers and the general public who are interested in anthropology and archaeology.

Acute Disorders of Consciousness in Pediatric Severe Sepsis and Organ Failure: Secondary Analysis of the Multicenter Phenotyping Sepsis-Induced Multiple Organ Failure Study.

OBJECTIVES: Acute disorders of consciousness (DoC) in pediatric severe sepsis are associated with increased risk of morbidity and mortality. We sought to examine the frequency of and factors associated with DoC in children with sepsis-induced organ failure. DESIGN: Secondary analysis of the multicenter Phenotyping Sepsis-Induced Multiple Organ Failure Study (PHENOMS). SETTING: Nine tertiary care PICUs in the United States. PATIENTS: Children less than 18 years old admitted to a PICU with severe sepsis and at least one organ failure during a PICU stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was frequency of DoC, defined as Glasgow Coma Scale (GCS) less than 12 in the absence of sedatives during an ICU stay, among children with severe sepsis and the following: single organ failure, nonphenotypeable multiple organ failure (MOF), MOF with one of the PHENOMS phenotypes (immunoparalysis-associated MOF [IPMOF], sequential liver failure-associated MOF, thrombocytopenia-associated MOF), or MOF with multiple phenotypes. A multivariable logistic regression analysis was performed to evaluate the association between clinical variables and organ failure groups with DoC. Of 401 children studied, 71 (18%) presented with DoC. Children presenting with DoC were older (median 8 vs 5 yr; p = 0.023), had increased hospital mortality (21% vs 10%; p = 0.011), and more frequently presented with both any MOF (93% vs 71%; p < 0.001) and macrophage activation syndrome (14% vs 4%; p = 0.004). Among children with any MOF, those presenting with DoC most frequently had nonphenotypeable MOF and IPMOF (52% and 34%, respectively). In the multivariable analysis, older age (odds ratio, 1.07; 95% CI, 1.01-1.12) and any MOF (3.22 [1.19-8.70]) were associated with DoC. CONCLUSIONS: One of every five children with severe sepsis and organ failure experienced acute DoC during their PICU stay. Preliminary findings suggest the need for prospective evaluation of DoC in children with sepsis and MOF.

WT1 as a myoepithelial marker: a comparative study of breast, cutaneous, and salivary gland lesions.

WT1 immunostain is expressed in various benign and malignant neoplasms, as well as normal myoepithelial cells. WT1 shows differential expression in non-neoplastic, benign, and malignant neoplastic myoepithelial cells of the salivary gland. In this study, WT1 immunostain and other myoepithelial markers were compared to investigate the value of WT1 as a myoepithelial marker, and to delineate the expression profile of WT1 in nonsalivary gland myoepithelial cells. WT1, p63, and calponin immunostains were performed on normal and lesional tissues from the breast (adenosis, sclerosing adenosis, lactating adenoma, nipple adenoma, tubular adenoma, adenomyoepithelioma, and adenoid cystic carcinoma [ACC]), skin (cutaneous mixed tumor, hidradenoma, spiradenoma, and ACC), and salivary gland (pleomorphic adenoma and ACC). The stained slides were digitized and orientated with H&E images and assessed simultaneously using QuPath. A total of 129, 58, and 56 breast, cutaneous, and salivary gland lesions, respectively, were included. There was poor agreement between WT1-p63 and WT1-calponin (κ < 0.1) in all organs, with absence of WT1 expression in normal salivary gland myoepithelium and most ACCs. There were no significant differences in WT1 expression in myoepithelial cells in normal breast tissue and benign breast neoplasms. Compared to pleomorphic adenomas, cutaneous mixed tumors showed lower WT1 expression (P < .001). WT1 is a less sensitive myoepithelial marker than calponin and p63. However, its unique pattern of expression in salivary gland primary for pleomorphic adenomas/cutaneous mixed tumor can favor a diagnosis of benign salivary gland tumors, particularly in small biopsy specimens.

A rare presentation of pemphigus vegetans as an isolated vegetative lesion-Review of histopathological clues and treatment effects in multiple biopsy specimens.

BACKGROUND: Pemphigus is a group of immunobullous dermatoses characterized by the presence of autoantibodies directed against adhesion molecules of keratinocytes, with pemphigus vegetans being the rarest form, accounting for 1%-2% of all cases of pemphigus. Pemphigus vegetans is characterized by verrucous vegetative lesions in addition to vesiculobullous lesions. METHODS: We report a rare case of pemphigus vegetans presenting as an isolated vegetative lesion in the groin 3 months prior to the development of blisters. Owing to the atypical presentation, multiple biopsies were performed before and after corticosteroid treatment. RESULTS: Comparing the histopathology of pre-treatment and post-treatment biopsy specimens, the resolution of intraepidermal microabscesses, and reduction in intraepidermal and dermal inflammatory infiltrates, spongiosis and interface change, attributable to treatment, were noted. However, direct immunofluorescence showed persistent intracellular intraepidermal deposition of IgG and C3 2 weeks into treatment, despite near-complete resolution of blisters on clinical examination. Clinical regression of the vegetative lesion was noted only after 6 weeks into corticosteroid treatment, while histopathological evidence of treatment was apparent at the second week. CONCLUSION: The current case illustrates the importance of a liberal use of immunofluorescence studies in establishing the uncommon yet significant diagnosis of pemphigus vegetans, particularly for vegetative lesions that are persistent, in the intertriginous areas and/or in the setting of concurrent cutaneous or mucosal symptoms.

The population genomic legacy of the second plague pandemic.

Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%-40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th-19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.

Micro-punches versus micro-slices for serial sampling of human dentine: Striking a balance between improved temporal resolution and measuring additional isotope systems.

RATIONALE: The last decade has seen a dramatic increase in the application of serial sampling of human dentine in archaeology. Rapid development in the field has provided many improvements in the methodology, in terms of both time resolution as well as the ability to integrate more isotope systems in the analysis. This study provides a comparison of two common sampling approaches, allowing researchers to select the most suitable approach for addressing specific research questions. METHODS: Two common approaches for sequential sampling of human dentine (micro-punches and micro-slices) are compared in terms of viability and efficacy. Using archaeological deciduous second molars and permanent first molars, this study demonstrates how the two approaches capture aspects of the weaning process in different ways. In addition, different aspects related to the extraction protocols, such as the thickness of the central slide and the solubilisation step, are also evaluated. RESULTS: While both approaches show similar intra-tooth isotopic patterns, the micro-punches approach is preferable for research that requires a very fine temporal resolution, while the micro-slices approach is best for research where δ34 S values are needed, or when the samples are poorly preserved. In addition, the solubilisation step has a large effect on collagen yield, and, to a lesser extent, on isotopic compositions. Therefore, it is important to ensure that only samples that have undergone the same pre-treatment protocol are directly compared. CONCLUSIONS: We present the pros and cons of the two micro-sampling approaches and offer possible mitigation strategies to address some of the most important issues related to each approach.

PRAME immunostain expression in sebaceous lesions, cutaneous carcinomas and adnexal structures.

The use of immunostain for PRAME antigen is well established for cutaneous melanolocytic lesions. However, its staining in other cutaneous structures and lesions is under reported. This study assessed PRAME staining in a large cohort of normal skin tissue, sebaceous lesions, and cutaneous carcinomas to better delineate patterns of PRAME immunoreactivity. PRAME immunostaining was performed on sections of sebaceous lesions and tissue microarrays of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). Normal cutaneous adnexal structures were assessed on the sections of sebaceous lesions. For sebaceous lesions and non-lesional sebaceous glands, PRAME immunostaining was assessed for mature, germinative and sebocytes independently. A total of 193 sebaceous lesions, 64 BCCs and 35 SCCs were stained for PRAME immunostain. Staining pattern was predominantly cytoplasmic in normal apocrine glands, germinative sebocytes of sebaceous glands, and hair germs (p<0.001). Lesional sebocytes did not show different staining compared to normal sebaceous glands (p>0.05). Rare nuclear staining was observed in the normal epidermis (0.6%) and junctional melanocytes (4.1%). BCC, SCC and sebaceous carcinoma all showed low levels of PRAME immunoreactivity with variable proportions of cases demonstrating nuclear staining (BCC 59.4%, SCC 37.1%, sebaceous carcinoma 5.3%). PRAME immunostaining is positive in germinative sebocytes, various cutaneous structures and carcinomas. Nuclear staining, identical to melanoma, was observed in normal epidermis, junctional melanocytes, BCCs, SCCs, and sebaceous carcinomas. The pattern of PRAME staining in the skin must be recognised to avoid pitfalls in interpretating PRAME immunostain.

Strontium isotope analyses of archaeological cremated remains - new data and perspectives.

Cremated human remains are commonly found in the archaeological records, especially in Europe during the Metal Ages and the Roman period. Due to the high temperatures reached during cremation (up to 1000°C), most biological information locked in the isotopic composition of different tissues is heavily altered or even destroyed. The recent demonstration that strontium isotope ratio (87Sr/86Sr) remain unaltered during cremation and are even very resistant to post-burial alterations (which is not the case in unburned bone), opened new possibility for palaeomobility studies of ancient populations that practice cremations as a funerary ritual. This paper summarizes strontium isotopic data produced over the last decade which is then deposited on the open-access platform IsoArcH (https://isoarch.eu/) for any interested parties to use. It is the first time isotopic data on cremated remains is introduced in this database, significantly extending its impact on the scientific community.

Four millennia of long-term individual foraging site fidelity in a highly migratory marine predator.

Theory and field studies suggest that long-term individual foraging site fidelity (IFSF) may be an important adaptation to competition from increasing population. However, the driving mechanisms and extent of long-term IFSF in wild populations of long-lived, migratory animals has been logistically difficult to study, with only a few confirmed instances. Temporal isotopic datasets can reveal long-term patterns in geographical foraging behaviour. We investigate the isotopic compositions of endangered short-tailed albatross (Phoebastria albatrus) over four millennia leading up to their near-extinction. Although not exhibited by short-tailed albatross today, we show past sub-populations displayed a high-degree of long-term IFSF, focusing on the same locations for hundreds of generations. This is the first large-scale evidence for the deep antiquity of long-term IFSF and suggests that it's density-driven. Globally, as populations of species like short-tailed albatross continue to recover from overexploitation, potential for resurgence of geographic specialization may increase exposure to localized hazards, requiring closer conservation monitoring.

Pediatric Intussusception Following COVID-19 Infection: A Rare Presentation.

Pediatric intussusception has been reported to be associated with coronavirus disease 2019 (COVID-19) infection in the literature since the start of the pandemic in the past two years. Although this occurrence is exceptionally rare, rapid diagnosis based on recognition of gastrointestinal manifestations, clinical examination, and ultrasound confirmation can expedite appropriate care and prevent delayed complications. Intussusception is the most common cause of intestinal obstruction and acute abdomen in pediatric patients. Without prompt identification, the disease process can lead to necrosis, bowel perforation, shock, and, subsequently, multiorgan failure. Intussusception has previously been associated with viral upper respiratory infections, which can cause mesenteric lymphadenopathy as a lead point to allow the bowel to telescope upon itself. The mechanism of how COVID-19 can contribute to intussusception without respiratory symptoms remains unknown. Here, we present a case of pediatric intussusception associated with COVID-19.

Incremental enamel and dentine isotopic data of faunal remains from the United Kingdom.

This paper collates previously published data from incremental isotopic studies performed on faunal remains found within the modern boundaries of the United Kingdom (UK). The dataset represents a complete collection of zooarchaeological incremental data from the UK, consisting of 1,092 data points, obtained from 152 faunal specimens from 20 archaeological sites, dating from 7960 BC to AD 1300. 59 of these values are from incrementally sampled dentine and present stable carbon and nitrogen isotope ratios (δ 13C and δ 15N). The remaining 1,053 values are from incrementally sampled enamel, and present strontium (87Sr/86Sr, n= 193), and/or stable carbon and oxygen isotope ratios (δ 13C and δ 18O, n = 860). This dataset is a convenient resource for future researchers, enabling comparisons based on faunal species, time, and geographical location. Further, the dataset acts as a mechanism for researchers to investigate the variety of incremental sampling methodologies (enamel and dentine) which have been applied to faunal remains across the United Kingdom. For ease of access, this dataset has been deposited on the open-access platform IsoArcH (https://isoarch.eu/).

Emergent needle thoracostomy in prehospital trauma patients: a review of procedural execution through computed tomography scans.

BACKGROUND: Traumatic tension pneumothoraces (TPT) are among the most serious causes of death in traumatic injuries, requiring immediate treatment with a needle thoracostomy (NT). Improperly placed NT insertion into the pleural cavity may fail to treat a life-threatening TPT. This study aimed to assess the accuracy of prehospital NT placements by paramedics in adult trauma patients. METHODS: A retrospective chart review was performed on 84 consecutive trauma patients who had received NT by prehospital personnel. The primary outcome was the accuracy of NT placement by prehospital personnel. Comparisons of various variables were conducted between those who survived and those who died, and proper versus improper needle insertion separately. RESULTS: Proper NT placement into the pleural cavity was noted in 27.4% of adult trauma patients. In addition, more than 19% of the procedures performed by the prehospital providers appeared to have not been medically indicated. DISCUSSION: Long-term strategies may be needed to improve the capabilities and performance of prehospital providers' capabilities in this delicate life-saving procedure. LEVEL OF EVIDENCE: IV.

Collagen stable isotope data from East and Northeast Asia, c. 7000 BC-1000 AD.

Stable isotope analysis is routinely used in archaeology to answer questions related to past diets. As the technique matures, data from archaeological sites have been generated at an exponential rate over the past several decades, thus provided an invaluable opportunity to examine past dietary practices and subsistence economies in much larger geographical and temporal settings. In Asia, a significant proportion of isotopic data is published in non-English journals or in grey literature, therefore remains largely inaccessible to general researchers. In order to provide easier access to these data, and to encourage future large-scale meta-data analyses in Asia, this collection presents the most comprehensive set of collagen stable isotope data of carbon, nitrogen, and sulfur from East and Northeast Asia (29-51˚N, 96-136˚ E) to date, including sites located within the modern territories of the People's Republic of China, Mongolia, the Russian Federation, and the Republic of Korea. Using academic search engines such as Google Scholar, the Chinese National Knowledge Infrastructure (CNKI), and ScienceON, a total of 3,304 previously published archaeological human and faunal stable isotope data from 136 archaeological sites in East and Northeast Asia, spanning over a period of 8,000 years (c. 7000 BC to AD 1000) are collected. The collated data are deposited on the open-access platform IsoArcH (https://isoarch.eu/) for any interested parties to use.

Stable isotope analysis of human bone from Ganj Dareh, Iran, ca. 10,100 calBP.

We report here on stable carbon, nitrogen, and sulfur isotope values from bone collagen of human (n = 20) and faunal (n = 11) remains from the Early Neolithic site of Ganj Dareh, Iran, dating to ca. 10,100 cal. BP. Our focus explores how isotope values of human bone vary by age and sex, and evaluates dietary practices at this site. It also provides a baseline for future studies of subsistence in the early Holocene Central Zagros Mountains, from the site with the first evidence for human ovicaprid management in the Near East. Human remains include individuals of all age groups for dietary reconstruction, as well two Ottoman intrusive burials for temporal and cultural comparison. All analyzed individuals exhibited δ13C and δ15N values consistent with a diet based heavily on C3 terrestrial sources. There is no statistically significant difference between the isotopic compositions of the two sexes, though males appear to show larger variations compared to females. Interesting patterns in the isotopic compositions of the subadults suggested weaning children may be fed with supplements with distinctive δ13C values. Significant difference in sulfur isotope values between humans and fauna could be the earliest evidence of transhumance and could identify one older adult male as a possible transhumant shepherd. Both Ottoman individuals had distinctively different δ13C, δ15N, and δ34S values compared to the Neolithic individuals. This is the first large scale analysis of human stable isotopes from the eastern end of the early Holocene Fertile Crescent. It provides a baseline for future intersite exploration of stable isotopes and insight into the lifeways, health, and processes of neolithisation associated with the origins of goat domestication at Ganj Dareh and the surrounding Central Zagros.

Stable isotope and dental caries data reveal abrupt changes in subsistence economy in ancient China in response to global climate change.

Prior to the introduction of wheat and barley from Central Asia during the Neolithic period, northern Chinese agricultural groups subsisted heavily on millet. Despite being the focus of many decades of intensive interest and research, the exact route(s), date(s), and mechanisms of the spread and adoption of wheat and barley into the existing well-established millet-based diet in northern China are still debated. As the majority of the important introduced crops are C3 plants, while the indigenous millet is C4, archaeologists can effectively identify the consumption of any introduced crops using stable carbon isotope analysis. Here we examine published stable isotope and dental caries data of human skeletal remains from 77 archaeological sites across northern and northwestern China. These sites date between 9000 to 1750 BP, encompassing the period from the beginning of agriculture to wheat's emergence as a staple crop in northern China. The aim of this study is to evaluate the implications of the spread and adoption of these crops in ancient China. Detailed analysis of human bone collagen δ13C values reveals an almost concurrent shift from a C4-based to a mixed C3/ C4- based subsistence economy across all regions at around 4500-4000 BP. This coincided with a global climatic event, Holocene Event 3 at 4200 BP, suggesting that the sudden change in subsistence economy across northern and northwestern China was likely related to climate change. Moreover, the substantially increased prevalence of dental caries from pre-to post-4000 BP indicates an increase in the consumption of cariogenic cereals during the later period. The results from this study have significant implications for understanding how the adoption of a staple crop can be indicative of large-scale environmental and socio-political changes in a region.