bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the Placental Biology of Tobacco Smoke, Nicotine, and Marijuana (THC) Exposures During Pregnancy
Authors: BANERJEE SOHINI , DEACON ALYSSA , SUTER MELISSA A. , AAGAARD KJERSTI M.
Published: February 2022

Widespread public health campaigns have reduces the prevalence of tobacco and nicotine exposures during pregnancy in the United States. However, tobacco and nicotine exposures during pregnancy persist as a common modifiable perinatal risk exposure. Furthermore, declines in tobacco use have been accompanied by parallel rises in both the prevalence and incidence of marijuana use in pregnancy. This is worrisome, as the macromolecules which comprise tobacco and marijuana smoke affect placental function. In this chapter we summarize the decades of evidence contributing to our understanding of the placental molecular pathophysiology accompanying these chemical exposures, thereby rendering risk of adverse perinatal outcomes.
Animal Models Evaluating the Impact of Prenatal Exposure to Tobacco and Marijuana
Authors: OLYAEI AMY F. , CAMPBELL LILY R. , ROBERTS VICTORIA H.J. , LO JAMIE O.
Published: February 2022

Within this review, the literature and outcomes from animal models of maternal marijuana use and cigarette smoking are summarized. The existing data demonstrate that prenatal marijuana and nicotine exposure both have multifaceted adverse effects on maternal, gestational, placental, and fetal outcomes. These include placental function and development, fetal growth and birth weight, and offspring neurodevelopment.
A Risk Comparison between Lifestyle, Socioeconomic Status, and Radiation: A Cohort Study of Cancer Mortality among Japanese Nuclear Workers (J-EPISODE)
Authors: Kudo Shin’ichi , Nishide Akemi , Furuta Hiroshige , Ishizawa Noboru , Saigusa Shin
Published: February 2022

The health effects of low-dose radiation exposure have been a source of controversy. One possible reason is that epidemiological studies that compare radiation risk with other factors, such as lifestyle or socioeconomic status, have been limited. The aim of this study is to conduct a comparison of the cancer risk of mortality between radiation, lifestyle habits (such as smoking), and socioeconomic status (such as years of education) among Japanese nuclear workers. We assembled a cohort of 41,742 male nuclear workers in Japan who answered a lifestyle questionnaire survey conducted during 2003–2004. To exclude systematic errors caused by missing values, we used multiple imputation and Poisson regression to estimate relative risks and confidence intervals for lifestyle habits, socioeconomic status, and radiation. The total person-y from 2005 to 2010 were 215,000. The mean age and cumulative dose were 54.9 y and 24.8 mSv (10-y lagged dose), respectively. Significantly high relative risks were determined for smoking, alcohol consumption, frequency of medical examination, breakfast intake, sleep, and body mass index. Further, significantly high relative risks of radiation were shown for lung cancer and smoking-related cancers. Since the simultaneous inclusion of radiation and non-radiation variables in the model for relative risk (RR) calculation means that the calculated radiation RR is the result of adjustment by other variables, the risk of cancer from low-dose radiation, if any, is less than smoking and probably less than other lifestyle factors.
Neurobehavioral Symptoms and Heart Rate Variability: Feasibility of Remote Collection Using Mobile Health Technology
Authors: Nabasny Andrew , Rabinowitz Amanda , Wright Brittany , Wang Jijia , Preminger Samuel , Terhorst Lauren , Juengst Shannon B.
Published: February 2022

Objectives:

To determine the covariance of heart rate variability (HRV) and self-reported neurobehavioral symptoms after traumatic brain injury (TBI) collected using mobile health (mHealth) technology.

Setting:

Community.

Participants:

Adults with lifetime history of TBI (n = 52) and adults with no history of brain injury (n = 12).

Design:

Two-week prospective ecological momentary assessment study.

Main Measures:

Behavioral Assessment Screening Tool (BASTmHealth) subscales (Negative Affect, Fatigue, Executive Dysfunction, Substance Abuse, and Impulsivity) measured frequency of neurobehavioral symptoms via a RedCap link sent by text message. Resting HRV (root mean square of successive R-R interval differences) was measured for 5 minutes every morning upon waking using a commercially available heart rate monitor (Polar H10, paired with Elite HRV app).

Results:

Data for n = 48 (n = 38 with TBI; n = 10 without TBI) participants were included in covariance analyses, with average cross-correlation coefficients (0-day lag) varying greatly across participants. We found that the presence and direction of the relationship between HRV and neurobehavioral symptoms varied from person to person. Cross-correlation coefficients r ≤ −0.30, observed in 27.1% to 29.2% of participants for Negative Affect, Executive Dysfunction, and Fatigue, 22.9% of participants for Impulsivity, and only 10.4% of participants for Substance Abuse, supported our hypothesis that lower HRV would covary with more frequent symptoms. However, we also found 2.0% to 20.8% of participants had positive cross-correlations (r ≥ 0.30) across all subscales, indicating that higher HRV may sometimes correlate with more neurobehavioral symptoms, and 54.2% to 87.5% had no significant cross-correlations.

Conclusions:

It is generally feasible for community-dwelling adults with and without TBI to use a commercially available wearable device to capture daily HRV measures and to complete a short, electronic self-reported neurobehavioral symptom measure for a 2-week period. The covariance of HRV and neurobehavioral symptoms over time suggests that HRV could be used as a relevant physiological biomarker of neurobehavioral symptoms, though how it would be interpreted and used in practice would vary on a person-by-person and symptom domain basis and requires further study.
AUTOSOMAL DOMINANT MÜLLER CELL SHEEN DYSTROPHY
Authors: Dalma-Weiszhausz José , Chacón-Camacho Oscar , CHEVEZ-BARRIOS Patricia , Zenteno Juan C. , Franco-Cárdenas Valentina , García-Montaño Leopoldo A. , Pérez-Bravo Jehieli , García-Montalvo Iván A. , Jiménez-Sierra Juan M. , Dalma Alexander
Published: February 2022

Background:

Autosomal dominant Müller cell dystrophy is a rare condition we described in 1991. It is characterized by a striking sheen appearance on the retinal surface with progressive retinal changes leading to disorganization and atrophy with a decreased b-wave electroretinograms.

Materials and Methods:

We examined 45 members of a 4-generation family. Fifteen subjects from three generations were found with the disease, without gender predilection. Seven patients underwent ophthalmic examination including fundus examination, intravenous fluorescein angiogram, spectral-domain optical coherence tomography, and electroretinogram. Six patients have a 30-year follow-up. Histopathology examination was performed on eyes of the eldest patient. Whole exome sequencing was done in four affected subjects.

Results:

Findings include a decreased visual acuity, abnormal cellophane-like sheen of the vitreoretinal interface, a “plush” nerve fiber layer, and characteristic macular changes. Electroretinogram showed a selective b-wave diminution. Intravenous fluorescein angiogram presented perifoveal hyperfluorescence and capillary leakage. Spectral-domain optical coherence tomography revealed cavitations involving inner and later outer retinal layers with later disorganization. Histopathologic findings included Müller cell abnormalities with cystic disruption of inner retinal layers, pseudoexfoliation in anterior segment, and amyloidosis of extraocular vessels. Pedigree analysis suggests an autosomal dominant inheritance with late onset. DNA analysis demonstrated a previously undescribed heterozygous missense p.Glu109Val mutation in transthyretin.

Conclusion:

To the best of our knowledge, this is the first family reported with this disorder. Our data support the hypothesis that autosomal dominant Müller cell dystrophy is a distinct retinal dystrophy affecting Müller cells. Mutations in transthyretin gene may manifest as a predominantly retinal disorder.
DEVELOPMENT OF FOCAL CHOROIDAL EXCAVATION IN A CASE OF IDIOPATHIC CHOROIDAL NEOVASCULAR MEMBRANE
Authors: Mahendrakar Priyanka , Bhende Muna , Menon Rahul
Published: February 2022

Purpose:

The purpose of this study was to demonstrate the evolution of focal choroidal excavation in a 17-year-old girl on treatment for a choroidal neovascular membrane over a 6-year follow-up.

Methods:

Review of medical and imaging records of a 17-year-old girl who presented with a choroidal neovascular membrane in her left eye treated with multiple intravitreal antivascular endothelial growth factor injections over a period of 6 years.

Results:

The patient developed recurrent episodes of subretinal hemorrhage that were treated with antivascular endothelial growth factor injections. Over the follow-up period, swept source optical coherence tomography through the lesion revealed progressive reduction in size of the choroidal neovascular membrane complex with the development of acquired focal choroidal excavation.
Identification of plasma hsa_circ_0000190 and 0001649 as biomarkers for predicting the recurrence and treatment response of patients with oral squamous cell carcinoma
Authors: Hung Kai-Feng , Chen Bing-Hong , Wang Tsui-Ying , Yang Yi-Ping , Chien Yueh , Lo Jeng-Fan , Yang Lin , Peng Bou-Yue , Kao Shou-Yen , Wu Cheng-Hsien
Published: February 2022

Background:

Oral squamous cell carcinoma (OSCC) is a type of malignancy characterized by high relapse and recurrence rates in the late stage despite optimal surgical intervention and postoperative chemoradiotherapy. Because the management of relapse following definitive treatment is challenging, accurate risk stratification is of clinical significance to improve treatment outcomes. Circular RNAs (circRNAs) are noncoding RNAs featured with cell-type specificity and high stability, owing to their circular structure, making these molecules excellent biomarkers for a variety of diseases.

Methods:

The levels of hsa_circ_0000190 and 0001649 in plasma samples from 30 healthy controls and 66 OSCC patients were determined by droplet digital polymerase chain reaction. The same primer sets were used with PCR to examine the expression of these two circRNAs in cancerous and adjacent normal tissues. A receiver operating characteristics curve was generated to evaluate the diagnostic value. The Kaplan–Meier method with a log-rank test was used for survival analysis.

Results:

We identified two circRNAs as potential biomarkers for OSCC, showing that the plasma level of hsa_circ_0000190 was significantly decreased in the late stage and marginally correlated with the development of second primary OSCC. We also found that the decreased plasma hsa_circ_0001649 was correlated with the recurrence and poor prognosis of patients. Additionally, we found that high plasma hsa_circ_0000190, but not hsa_circ_0001649, possibly predicted a better response of patients to induction chemotherapy.

Conclusion:

Our study demonstrated the potential of biomarkers in plasma to inform not just the tumor but the entire oral cavity, thereby offering a prediction for early recurrence and second primary OSCC. The plasma circRNAs remain valuable for OSCC, albeit the easy accessibility to the oral cavity.
Spatial transcriptomics and the kidney
Authors: Melo Ferreira Ricardo , Gisch Debora L. , Eadon Michael T.
Published: February 2022

Purpose of review

The application of spatial transcriptomics technologies to the interrogation of kidney tissue is a burgeoning effort. These technologies share a common purpose in mapping both the expression of individual molecules and entire transcriptomic signatures of kidney cell types and structures. Such information is often superimposed upon a histologic image. The resulting datasets are readily merged with other imaging and transcriptomic techniques to establish a spatially anchored atlas of the kidney. This review provides an overview of the various spatial transcriptomic technologies and recent studies in kidney disease. Potential applications gleaned from the interrogation of other organ systems, but relative to the kidney, are also discussed.

Recent findings

Spatial transcriptomic technologies have enabled localization of whole transcriptome mRNA expression, correlation of mRNA to histology, measurement of in situ changes in expression across time, and even subcellular localization of transcripts within the kidney. These innovations continue to aid in the development of human cellular atlases of the kidney, the reclassification of disease, and the identification of important therapeutic targets.

Spatial localization of gene expression will complement our current understanding of disease derived from single cell RNA sequencing, histopathology, protein immunofluorescence, and electron microscopy. Although spatial technologies continue to evolve rapidly, their importance in the localization of disease signatures is already apparent. Further efforts are required to integrate whole transcriptome and subcellular expression signatures into the individualized assessment of human kidney disease.
Updating the healthcare maintenance visit for children with medical complexity: applying lessons learned from the coronavirus disease 2019 pandemic
Authors: Driansky Allison , Pilapil Mariecel , Mastrogiannis Ariana
Published: February 2022

Purpose of review

Coronavirus disease 2019 (COVID-19) has exposed the vulnerabilities of children with medical complexity (CMC). This article uniquely describes how pediatric providers in various clinical settings can adapt routine healthcare maintenance visits to meet the needs of CMC in the era of COVID-19. We also discuss unique visit components important to address when providing primary care to CMC, including caregiver support, disaster preparedness, long-term care planning, and telemedicine.

Recent findings

Although some children may be less severely affected by COVID-19 than adults, current literature suggests that CMC may be at higher risk for severe disease. In addition, the COVID-19 pandemic has highlighted the value in consistent, primary care for CMC. Children, especially those with medical complexity, are at risk for interruptions in care, delayed vaccinations, increasing caregiver burden, and barriers to in-person care.

This article summarizes the components of the healthcare maintenance visit for CMC, providing salient recommendations on how pediatric providers can adapt their approach to the primary care of CMC in the era of COVID-19.
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.

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.

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.
Regression in Early Childhood Development: An Unintended Outcome of Prolonged Hospitalization?
Authors: Dahl Claire M. , Kroupina Maria , Lone Diana W. , Greengard Emily , Somani Arif
Published: February 2022

This brief review outlines a novel case study with targeted literature search. Patient X was a 21-month-old male who was receiving ongoing treatment for stage M MYCN-amplified high-risk neuroblastoma. Patient X’s mother was considering refusal of further cancer-directed therapy because of the child’s developmental regression noted during his prolonged hospitalization. Given the underlying malleability of the developing brain in early childhood, access to supportive services that facilitate ongoing neurodevelopment in hospitalized young children is of utmost importance; such services further reduce parental stress and likely enhances parental and medical team efficacy of care.
Phyllodes Tumor as a Secondary Neoplasm in Survivors of Childhood Cancer: A Tertiary Care Cancer Centre Experience
Authors: Agrawal Radhika , Sahay Ayushi , Patil Asawari , Ramadwar Mukta , Prasad Maya , Popat Palak , Joshi Shalaka , Shet Tanuja , Desai Sangeeta
Published: February 2022

Secondary neoplasms (SNs) are being increasingly identified in long-term survivors of childhood cancer. Phyllodes tumor (PT) form a distinctly uncommon SN. We report a series of 6 female childhood cancer survivors who developed PT as SN. The median age at primary diagnosis was 13 years. Their primary tumors were bone sarcoma (4) and acute leukemia (2), and all were treated with chemotherapy, predominantly with alkylating agents and/or anthracyclines. None had received direct radiotherapy to the chest wall. Subsequently, PT were detected after a median interval of 7.5 years, with 2 patients developing bilateral and malignant PT. The series highlights a rare SN in childhood cancer survivors, underscoring the importance of regular long-term follow-up.
Response to Alpelisib in Clinically Distinct Pediatric Patients With PIK3CA-related Disorders
Authors: Kolitz Elysha , Fernandes Neil J. , Agim Nnenna G. , Ludwigl Kathleen
Published: February 2022

PIK3CA-related disorders include vascular malformations, potential overgrowth of various tissues, limb abnormalities, disordered soft tissue, and/or fatty hyperplasia that often leads to significant morbidity. Alpelisib, a targeted inhibitor of p110α, an enzyme encoded by the PIK3CA gene, has demonstrated success in a cohort of patients with PIK3CA-driven overgrowth syndromes. We describe the clinical course of 2 pediatric patients treated with alpelisib under the Novartis Managed Access Program. Both patients, though clinically distinct, demonstrate improvements in overgrowth volumes/extent, function of their affected limb, and quality of life, without significant adverse effects after prolonged treatment.
Pediatric Benign Neutropenia: Assessing Practice Preferences in Canada
Authors: Chok Rozalyn , Price Victoria , Steele MacGregor , Corriveau-Bourque Catherine , Bruce Aisha
Published: February 2022

Pediatric benign neutropenia is a self-limited condition with a benign clinical course. An approach to this condition is not well-defined in the literature. Our objective was to use a case-based survey to elucidate trends in the diagnosis and management of benign neutropenia among pediatric hematology/oncology practitioners in Canada. We received 46 completed surveys (response rate 66%). At initial presentation with fever and neutropenia, 67% of respondents recommended partial septic workup but 11% recommended no investigations. Nearly 70% recommended admission for empiric intravenous antibiotics, while 24% would discharge home without antibiotics. In a patient with fever and known neutropenia, respondents were more likely to pursue outpatient antibiotic therapy. For investigation of chronic neutropenia, most respondents (60%) do not use antineutrophil antibody testing. Common indications for bone marrow biopsy were severe infection, prolonged neutropenia, or before initiating granulocyte colony stimulating factor. Indications for granulocyte colony stimulating factor were based on severity and frequency of infection. Most respondents (84%) would not recommend antibiotic prophylaxis. Results demonstrate the considerable variability in management of benign neutropenia among pediatric hematology/oncology practitioners in Canada and highlight the need for prospective studies to establish diagnostic criteria for benign neutropenia and evaluate management of fever in this population.
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.
Recurrent Loss of Heterozygosity in Pancreatic Neuroendocrine Tumors
Authors: Parilla Megan , Chapel David , Hechtman Jaclyn F. , Wanjari Pankhuri , El Jabbour Tony , Sharma Aarti , Ritterhouse Lauren , Segal Jeremy , Vanderbilt Chad , Klimstra David S. , Setia Namrata , Tang Laura
Published: February 2022

Chromosomal aneuploidies are prognostic markers across a wide variety of tumor types, and recent literature suggests that pancreatic neuroendocrine tumors are no different. In this study 214 patients with grade 1, 2, or 3 pancreatic neuroendocrine tumors had their tissue examined for chromosomal copy number alterations using next-generation sequencing. Univariate and multivariate statistical analyses were performed with all-cause mortality and disease-specific mortality as the end comparators. As such, the cohort stratified into 3 different clinically relevant chromosomal subgroups: an indolent subgroup characterized by loss of chromosome 11 in relative isolation, an aggressive subgroup characterized by losses of chromosomes 1, 2, 3, 6, 10, 11, 16, and 22 and with no loss of chromosomes 4, 5, 7, 12, 14, 17, 19, and 20, and finally a heterogeneous third group with a subset of cases that behave even more aggressively than the aforementioned.
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’.
Two emetolite-pterosaur associations from the Late Jurassic of China: showing the first evidence for antiperistalsis in pterosaurs
Authors: Jiang Shunxing , Wang Xiaoli , Zheng Xiaoting , Cheng Xin , Wang Xiaolin , Wei Guangjin , Kellner Alexander W. A.
Published: February 2022

Knowledge about the pterosaur diet and digestive system is limited, and there is little direct evidence in the fossil record. Here, we report two specimens of the wukongopterid
Kunpengopterus sinensis
, a juvenile and an adult, from the Late Jurassic Yanliao Biota of China with associated bromalites. Both of these concentrations are identified as emetolites, fossilized gastric pellets. These pellets contain scales of an unnamed palaeonisciform fish, confirming the pterosaur was a piscivore. It probably vomited the pellets, indicating the presence of two-part stomachs and efficient antiperistalsis in both juveniles and adults. Comparing the ganoid scales found in the pellets with those of complete fishes, it was possible to determine that the prey of the smaller pellet is an average-sized individual, while the prey of the larger pellet represents a large specimen.
Kunpengopterus sinensis
might have preyed on the same fish during ontogeny, with adults being able to feed on larger individuals.

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

The 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

Kleefstra 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.
Resting State fMRI for Motor Cortex Mapping in Children with Epilepsy
Authors: Krishnamurthy Manu , You Xiaozhen , Sepeta Leigh N. , Matuska Emily , Oluigbo Chima , Berl Madison M. , Gaillard William D. , Gholipour Taha
Published: February 2022

Task-based fMRI is commonly used to localize motor functions prior to epilepsy surgery. Not all children are able to follow task instructions in the scanner, limiting fMRI motor mapping. We present a data-driven method to automatically delineate the motor cortex using task-free, resting state fMRI (rsfMRI) data of children with epilepsy and controls.

We preprocessed anatomical and rsfMRI images (64 patients, 12 controls) using fMRIPrep. We used FSL MELODIC tool for whole brain ICA estimation in multiple orders, to generate several sets of independent components. We defined a motor component selection process based on Discriminability Index-based Component Identification (DICI) score, resulting from comparing binarized component to the Human Motor Area Template (HMAT) in subject’s native brain space. Components with the largest DICI score and their peak in the template were combined to form the whole-brain ICA Motor Map (wIMM). We validated wIMM by comparing individual results with finger tapping motor task activation, and evaluated its reproducibility in controls with two runs of rsfMRI.

The hit rate between wIMM and motor task activation ranged 60 to 77% across all participants. Sensitivity of wIMM for capturing the task activation was 87.5% among 32 patients and 100% in 11 controls with available task results. The mean Dice similarity in results from repeated runs was 0.70 in controls.

Our results shows the sensitivity and reproducibility of an automated motor mapping based on ICA analysis of rsfMRI in children with epilepsy. The ICA maps may provide different, but useful, information than task fMRI. Future studies will expand our method to mapping other brain functions, and may lead to a surgical planning tool for patients who cannot perform task fMRI and help predict their postsurgical function.