bluuebunny/crossref_metadata_2025_split huggingface dataset:
Update on immunosuppressive strategies in intestinal transplantation
Authors: Merola Jonathan , Shamim Abrar , Weiner Joshua 
Published: February 2022

Purpose of review
The intestine is the most immunologically complex solid organ allograft with the greatest risk of both rejection and graft-versus-host disease (GVHD). High levels of immunosuppression are required, further increasing morbidity. Due to low volume of transplants and few centers with experience, there is paucity of evidence-based, standardized, and effective therapeutic regimens. We herein review the most recent data about immunosuppression, focusing on novel and emerging therapies.

Recent findings
Recent data are moving the field toward increasing use of basilixumab and consideration of alemtuzumab for induction and inclusion of mammalian target of rapamycin inhibitors and antimetabolites for maintenance. For rejection, we highlight novel roles for tumor necrosis factor-α inhibition, α4β7 integrin inhibition, microbiome modulation, desensitization protocols, and tolerance induction strategies. We also highlight emerging novel therapies for GVHD, especially the promising role of Janus kinase inhibition.

Summary
New insights into immune pathways associated with rejection and GVHD in intestinal allografts have led to an evolution of therapies from broad-based immunosuppression to more targeted strategies that hold promise for reducing morbidity from infection, rejection, and GVHD. These should be the focus of further study to facilitate their widespread use.
Current review on the role of ileostomy following intestinal transplantation
Authors: Venick Robert S. 
Published: February 2022

Purpose of review
This review describes the historical rationale for ostomy creation at the time of intestinal transplantation (ITx), examines the utility of endoscopy in graft monitoring, details the limitations and potential complications of endoscopy in this patient population, highlights preliminary reports of ITx without surveillance biopsy or stoma formation, and emphasizes the importance of novel biomarkers for graft monitoring. Data will be discussed from contemporary publications in the field, as well as the Intestinal Transplant Registry.

Recent findings
Significant improvements have been made in early outcomes following ITx, yet long-term survival remains challenged by rejection. Although endoscopy and biopsy are the gold-standard for graft monitoring, some centers have performed ITx recently without surveillance endoscopy or stoma formation with similar success. Others have touted the need for less-invasive, timely and accurate biomarkers as essential to help improve results.

Summary
The review provides a thorough overview of the emerging debate in the field of ITx regarding the importance of surveillance endoscopy and stoma formation in ITx recipients.
Designing and Implementing a Zero Harm Falls Prevention Program
Authors: Wilson Mary-Agnes , Hacker Teper Matthew , Sinno Maya , Kohlberger Kim , Nuseir Deema , Chan Angela , Palomera-Dinglasan Kristen , Leon Lauren , Donaldson Dawn , Taher Ahmed 
Published: February 2022

Background:
Inpatient falls with harm have severe implications on patients and the health care system.

Purpose:
We implemented a zero harm approach to falls prevention, which aimed to reduce falls with injury by 25% within 1 year.

Methods:
We implemented a multifaceted and multidisciplinary quality improvement falls prevention strategy that included facilitating organization-wide education, adopting the Morse Fall Risk Assessment tool, displaying real-time unit-specific falls rates, and implementing a transparent root-cause analysis process after falls. Our outcome measure was falls with injury per 1000 patient-days.

Results:
We observed a decrease in the rate of patient falls with injury from 2.03 (baseline period) to 1.12 (1 year later) per 1000 patient-days. We also observed increases in awareness around falls prevention and patient safety incident reporting.

Conclusions:
Our zero harm approach reduced falls with injury while improving our patient safety culture.
The Effect of HIV Programs in South Africa on National HIV Incidence Trends, 2000–2019
Authors: Johnson Leigh F. , Meyer-Rath Gesine , Dorrington Rob E. , Puren Adrian , Seathlodi Thapelo , Zuma Khangelani , Feizzadeh Ali 
Published: February 2022

Background:
Recent studies have shown HIV incidence declines at a population level in several African countries. However, these studies have not directly quantified the extent to which incidence declines are attributable to different HIV programs.

Methods:
We calibrated a mathematical model of the South African HIV epidemic to age- and sex-specific data from antenatal surveys, household surveys, and death registration, using a Bayesian approach. The model was also parameterized using data on self-reported condom use, voluntary medical male circumcision (VMMC), HIV testing, and antiretroviral treatment (ART). Model estimates of HIV incidence were compared against the incidence rates that would have been expected had each program not been implemented.

Results:
The model estimated incidence in 15–49 year olds of 0.84% (95% CI: 0.75% to 0.96%) at the start of 2019. This represents a 62% reduction (95% CI: 55% to 66%) relative to 2000, a 47% reduction (95% CI: 42% to 51%) relative to 2010, and a 73% reduction (95% CI: 68% to 77%) relative to the incidence that would have been expected in 2019 in the absence of any interventions. The reduction in incidence in 2019 because of interventions was greatest for ART and condom promotion, with VMMC and behavior change after HIV testing having relatively modest impacts. HIV program impacts differed significantly by age and sex, with condoms and VMMC having greatest impact in youth, and overall incidence reductions being greater in men than in women.

Conclusions:
HIV incidence in South Africa has declined substantially since 2000, with ART and condom promotion contributing most significantly to this decline.
Believing That It Is Hazardous to Mix Alcohol With Medicines Predicts Intentional Nonadherence to Antiretrovirals
Authors: Kalichman Seth C. , Eaton Lisa A. , Kalichman Moira O. 
Published: February 2022

Background:
Drinking alcohol is a robust predictor of medication nonadherence. In addition to the impact of intoxication on adherence, individuals who believe that it is hazardous to mix medications with alcohol (ie, interactive toxicity beliefs) may forgo taking their medications when drinking. Previous research suggests that alcohol-related intentional nonadherence is a direct result of interactive toxicity beliefs. This study prospectively tested the association between alcohol interactive toxicity beliefs and intentional nonadherence to HIV treatment [ie, antiretroviral therapy (ART)].

Methods:
Four hundred eight people living with HIV completed comprehensive baseline assessments and 15-month attributions for ART nonadherence.

Results:
One in 5 participants reported foregoing taking their ART when drinking out of concern for hazardous mixing of alcohol and ART. Poisson regression models predicting the number of months that participants were intentionally nonadherent to ART because they were drinking was predicted by alcohol-ART interactive toxicity beliefs.

Conclusions:
Beliefs that it is hazardous to drink alcohol when taking medications explains intentional nonadherence and should be directly addressed in adherence improvement interventions for people living with HIV who drink alcohol.
HIV-Associated Neurocognitive Disorders: The First Longitudinal Follow-Up of a cART-Treated Cohort of Older People in Sub-Saharan Africa
Authors: Spooner Rebecca , Ranasinghe Sherika , Urasa Sarah , Yoseph Marcella , Koipapi Sengua , Mukaetova-Ladinska Elizabeta B. , Lewis Thomas , Howlett William , Dekker Marieke , Kisoli Aloyce , Gray William K. , Walker Richard W. , Dotchin Catherine L. , Kalaria Raj , Lwezuala Bingileki , Makupa Philip C. , Akinyemi Rufus , Paddick Stella M. 
Published: February 2022

Background:
HIV-associated neurocognitive disorders (HAND) are a highly prevalent chronic complication in older people living with HIV (PLWH) in high-income countries. Although sub-Saharan Africa has a newly emergent population of older combination antiretroviral therapy (cART)-treated PLWH, HAND have not been studied longitudinally. We assessed longitudinal prevalence of HAND and have identified possible modifiable factors in a population of PLWH aged 50 years or older, over 3 years of follow-up.

Methods:
Detailed neuropsychological and clinical assessment was completed annually in the period 2016–2019 in a systematic sample of cART-treated PLWH in Kilimanjaro, Tanzania. A consensus panel defined HAND using American Academy of Neurology criteria for asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia. HIV disease severity and other factors associated with HAND progression, improvement, and stability were evaluated in individuals fully assessed at baseline and in 2019.

Results:
At baseline, 47% of the cohort (n = 253, 72.3% female individuals) met HAND criteria despite good HIV disease control [Y1 59.5% (n = 185), Y2 61.7% (n = 162), and Y3 57.9% (n = 121)]. Of participants fully assessed at baseline and year 3 (n = 121), HAND remained stable in 54% (n = 57), improved in 15% (n = 16), and declined in 31% (n = 33). Older age and lower education level significantly predicted HAND progression, whereas HIV-specific factors did not. Male sex and shorter cART duration were associated with improvement.

Conclusions:
In this first longitudinal study characterizing clinical course of HAND in older cART-treated PLWH in sub-Saharan Africa, HAND was highly prevalent with variable progression and reversibility. Progression may be more related to cognitive reserve than HIV disease in cART-treated PLWH.
The 35-mm rule to guide pneumothorax management: Increases appropriate observation and decreases unnecessary chest tubes
Authors: Figueroa Juan F. , Karam Basil S. , Gomez Jose , Milia David , Morris Rachel S. , Dodgion Christopher , Carver Thomas , Murphy Patrick , Elegbede Anuoluwapo , Schroeder Mary , de Moya Marc A. 
Published: February 2022

INTRODUCTION
Axial imaging has allowed for more precise measurement and, in-turn, more objective guidelines related to the management of traumatic pneumothoraces (PTXs). In 2017, our trauma center used a guideline to observe any PTX ≤35 mm in stable patients. We hypothesize that this guideline would decrease unnecessary chest tubes without affecting failure rates.

METHODS
This is a single-center retrospective review of all adult trauma patients who had a PTX diagnosed on computed tomography before (2015–2016) and after (2018–2019) guideline implementation. We excluded patients with chest tubes inserted before computed tomography, concurrent hemothoraces, mechanical ventilation, or mortality in the first 24 hours. Descriptive statistical analyses, χ2 test, and Mann-Whitney U test were performed as appropriate.

RESULTS
A total of 266 patients met our inclusion criteria. Ninety-nine (37.2%) and 167 patients (62.7%) were admitted before and after 2017, respectively. Overall, there were no differences in demographics or severity of injuries between both groups. After guideline implementation, there was a significant increase in observation rates and compliance rate. Tube thoracostomies decreased from 28.3% to 18% (p = 0.04). There were no statistically significant changes in observation failure rates, hospital or intensive care unit length of stay, complications, or mortality.

CONCLUSION
The implementation of the 35 mm guideline is an effective tool to decrease unnecessary tube thoracostomy in hemodynamically normal patients without evidence of hemothorax.

LEVEL OF EVIDENCE
Therapeutic/care management, level III.
Diverse and complex developmental mechanisms of early Ediacaran embryo-like fossils from the Weng'an Biota, southwest China
Authors: Yin Zongjun , Sun Weichen , Liu Pengju , Chen Junyuan , Bottjer David J. , Li Jinhua , Zhu Maoyan 
Published: February 2022

The origin and early evolution of animal development remain among the many deep, unresolved problems in evolutionary biology. As a compelling case for the existence of pre-Cambrian animals, the Ediacaran embryo-like fossils (EELFs) from the Weng'an Biota (approx. 609 Myr old, Doushantuo Formation, South China) have great potential to cast light on the origin and early evolution of animal development. However, their biological implications can be fully realized only when their phylogenetic positions are correctly established, and unfortunately, this is the key problem under debate. As a significant feature of developmental biology, the cell division pattern (CDP) characterized by the dynamic spatial arrangement of cells and associated developmental mechanisms is critical to reassess these hypotheses and evaluate the diversity of the EELFs; however, their phylogenetic implications have not been fully realized. Additionally, the scarcity of fossil specimens representing late developmental stages with cell differentiation accounts for much of this debate too. Here, we reconstructed a large number of EELFs using submicron resolution X-ray tomographic microscopy and focused on the CDPs and associated developmental mechanisms as well as features of cell differentiation. Four types of CDPs and specimens with cell differentiation were identified. Contrary to the prevailing view, our results together with recent studies suggest that the diversity and complexity of developmental mechanisms documented by the EELFs are much higher than is often claimed. The diverse CDPs and associated development features including palintomic cleavage, maternal nutrition, asymmetric cell divisions, symmetry breaking, establishment of polarity or axis, spatial cell migration and differentiation constrain some, if not all, EELFs as total-group metazoans.This article is part of the theme issue ‘The impact of Chinese palaeontology on evolutionary research’.
The evolution of biramous appendages revealed by a carapace-bearing Cambrian arthropod
Authors: Fu Dongjing , Legg David A. , Daley Allison C. , Budd Graham E. , Wu Yu , Zhang Xingliang 
Published: February 2022

Biramous appendages are a common feature among modern marine arthropods that evolved deep in arthropod phylogeny. The branched appendage of Cambrian arthropods has long been considered as the ancient biramous limb, sparking numerous investigations on its origin and evolution. Here, we report a new arthropod,Erratus speraregen. et sp. nov., from the Lower Cambrian (Stage 3, 520 Ma) Chengjiang biota of Yunnan, China, with unique trunk appendages formed of lateral anomalocaridid-type flaps and ventral subconical endopods. These appendages represent an intermediate stage of biramous limb evolution, i.e. from ‘two pairs of flap appendages' in radiodonts to ‘flap + endopod’ inErratus, to ‘exopod + endopod’ in the rest of carapace-bearing arthropods that populate the basal region of the upper-stem lineage arthropods (deuteropods). The new species occupies a phylogenetic position at the first node closer to deuteropods than to radiodonts, and therefore pinpoints the earliest occurrence of the endopod within Deuteropoda. The primitive endopod is weakly sclerotized, and has unspecialized segments without endites or claw. The findings might support previous claims that the outer branch of the biramous limb of fossil marine arthropods, such as trilobites, is not a true exopod, but is instead a modified exite.This article is part of the theme issue ‘The impact of Chinese palaeontology on evolutionary research’.
Aposematic coloration from Mid-Cretaceous Kachin amber
Authors: Xu Chunpeng , Luo Cihang , Jarzembowski Edmund A. , Fang Yan , Wang Bo 
Published: February 2022

Aposematic coloration is among the most diverse antipredator strategies, which can signal unpleasantness of organisms to potential predators and reduce the probability of predation. Unlike mimesis, aposematic coloration allows organisms to warn their predators away by conspicuous and recognizable colour patterns. However, aposematism has been a regular puzzle, especially as the long-term history of such traits is obscured by an insufficient fossil record. Here, we report the discovery of aposematic coloration in an orthopteran nymph from Mid-Cretaceous Kachin amber (99 million years old). It is attributed to the extinct family Elcanidae and erected as a new genus identified by conspicuous dark/light-striped coloration, four apical spurs on the metatibia, a two-segmented metatarsus and unsegmented stylus. It represents the first fossil orthopteran preserved with aposematic coloration from the Mesozoic, demonstrating that orthopterans had evolved aposematism by the Mid-Cretaceous. Our findings provide novel insights into the early evolution of anti-predator strategies among orthopterans. Together with mimesis, debris-carrying camouflage and aposematism previously reported, our findings demonstrate the relative complexity of prey–predator interactions in the Mesozoic, especially in the Mid-Cretaceous Kachin amber forest.
This article is part of the theme issue ‘The impact of Chinese palaeontology on evolutionary research’.
A new mammal from the Lower Cretaceous Jehol Biota and implications for eutherian evolution
Authors: Wang Hai-Bing , Hoffmann Simone , Wang Dian-Can , Wang Yuan-Qing 
Published: February 2022

Here we report on a new Early Cretaceous eutherian represented by a partial skeleton from the Jiufotang Formation at Sihedang site, Lingyuan City, Liaoning Province that fills a crucial gap between the earliest eutherians from the Yixian Formation and later Cretaceous eutherians. The new specimen reveals, to our knowledge for the first time in eutherians, that the Meckelian cartilage was ossified but reduced in size, confirming a complete detachment of the middle ear from the lower jaw. Seven hyoid elements, including paired stylohyals, epihyals and thyrohyals and the single basihyal are preserved. For the inner ear the ossified primary lamina, base of the secondary lamina, ossified cochlear ganglion and secondary crus commune are present and the cochlear canal is coiled through 360°. In addition, plesiomorphic features of the dentition include weak conules, lack of pre- and post-cingula and less expanded protocones on the upper molars and height differential between the trigonid and talonid, a large protoconid and a small paraconid on the lower molars. The new taxon displays an alternating pattern of tooth replacement with P3 being the last upper premolar to erupt similar to the basal eutherianJuramaia. Parsimony analysis places the new taxon withMontanalestes,SinodelphysandAmbolestesas a sister group to other eutherians.This article is part of the theme issue ‘The impact of Chinese palaeontology on evolutionary research’.
New insights into the South China Lower Devonian flora based on fossils from Hezhang, Guizhou Province
Authors: Wang Yao , Bai Jiao , Liu Bing-Cai , Wang Yi , Xu Hong-He 
Published: February 2022

The Early Devonian flora of South China is composed of many endemic members and has been studied mainly based on Yunnan materials. We in this study report a new Lower Devonian plant locality, recognize four sub-regions of the Early Devonian flora from South China and furthermore demonstrate these plants' distribution pattern and probable dispersal route. The new finds of plant fossils are from the Lower Devonian of Hezhang County, Guizhou Province, and include ZosterophyllopsidaDemersathecaand EuphyllophytopsidaPauthecophyton.Demersatheca contigua, consisting of cylindrical strobili with four longitudinal rows of sporangia decussately arranged, shows great similarities to the plant from Yunnan and Guangxi localities.Pauthecophyton hezhangensissp. nov. has distinct fertile units with grouped sporangia and each unit with two or three fusiform sporangia. The new locality belongs to the Guizhou sub-region and shares some taxa with the eastern Yunnan and Cathaysia sub-regional floras within South China, in which the shared plant members are distributed around the epicontinental sea. We suggest that the Guizhou sub-region might act as a bridge during plant dispersal from eastern Yunnan to Cathaysia Oldland in the Early Devonian.This article is part of the theme issue ‘The impact of Chinese palaeontology on evolutionary research’.
RaPID-Query for Fast Identity by Descent Search and Genealogical Analysis
Authors: Wei Yuan , Naseri Ardalan , Zhi Degui , Zhang Shaojie 
Published: February 2022

AbstractThe size of genetic databases has grown large enough such that, genetic genealogical search, a process of inferring familial relatedness by identifying DNA matches, has become a viable approach to help individuals finding missing family members or law enforcement agencies locating suspects. However, a fast and accurate method is needed to search an out-of-database individual against millions of individuals in such databases. Most existing approaches only offer all-vs-all within panel match. Some prototype algorithms offer 1-vs-all query from out-of-panel individual, but they do not tolerate errors. A new method, random projection-based identical-by-descent (IBD) detection (RaPID) query, referred as RaPID-Query, is introduced to make fast genealogical search possible. RaPID-Query method identifies IBD segments between a query haplotype and a panel of haplotypes. By integrating matches over multiple PBWT indexes, RaPID-Query method is able to locate IBD segments quickly with a given cutoff length while allowing mismatched sites in IBD segments. A single query against all UK biobank autosomal chromosomes can be completed within 2.76 seconds CPU time on average, with the minimum 7 cM IBD segment length and minimum 700 markers. Using the same criteria, RaPID-Query can achieve 0.099 false negative rate and 0.017 false positive rate at the same time on a chromosome 20 sequencing panel having 92,296 sites, which is comparable to the state-of-the-art IBD detection method Hap-IBD. For the relatedness degree separation experiments, RaPID-Query is able to distinguish up to fourth degree of the familial relatedness for a given individual pair, and the area under the receiver operating characteristic curve values are at least 97.28%. It is anticipated that RaPID-Query will make genealogical search convenient and effective, potentially with the integration of complex inference models.
Defensive and offensive behaviors in social interaction settings in a Kleefstra syndrome mouse model
Authors: Alonso Alejandra , Samanta Anumita , van der Meij Jacqueline , van den Brand Liz , Negwer Moritz , Lobato Irene Navarro , Genzel Lisa 
Published: February 2022

AbstractKleefstra syndrome in humans is characterized by general delay in development, intellectual disability and autistic features. The mouse model of this disease (Ehmt1+/-) expresses anxiety, autistic-like traits, and aberrant social interactions with non-cagemates. To investigate how Ehmt1+/- mice behave with unfamiliar conspecifics, we allowed adult, male animals to freely interact for 10 minutes in a neutral, novel environment within a host-visitor setting. In 17 out of 74 trials there were defensive and offensive behaviors. Our key finding was that Ehmt1+/- mice displayed defensive postures, attacking and biting; in contrast, wild-type (WT) interacting with other WT did not enact such behaviors. Further, if there was a fight between an Ehmt1+/- and a WT mouse, it was always the Ehmt1+/- who initiated these behaviors.