bluuebunny/crossref_metadata_2025 huggingface dataset:
The Hoabinhian: The Late and Post-Pleistocene Cultural Systems of Southeast Asia
Authors: Shoocongdej Rasmi
Published: February 2022

This chapter reviews the current state of knowledge regarding the Hoabinhian in the context of Southeast Asian prehistory, including the variability and distribution of Hoabinhian sites and assemblages and the nature and significance of archaeological data from the Late Pleistocene and Post-Pleistocene in Mainland Southeast Asia. The term “Hoabinhian” was initially applied during the Colonial Period to hunter-gatherer sites, mainly caves, located in Hoa Binh Province of northern Vietnam. Based largely on stone tool morphology, Hoabinhian sites are now widely distributed across Southeast Asia and southern China. Only a few excavated sites have been securely dated, and so, relative dating remains the main chronological approach, based on formal typological criteria. A simple definition of the Hoabinhian concept with regard to tool types should be reevaluated. However, new discoveries have suggested a holistic view of Late Pleistocene and Holocene culture as the analytical methods of explaining how cultural systems work within obvious limitations balance the attention focused on technologies.
Characteristics and outcomes of patients with heart failure discharged from different speciality units in Australia: an observational study
Authors: Sharma Y , Horwood C , Hakendorf P , Thompson C
Published: February 2022

Background

Previous studies have reported differing clinical outcomes among hospitalized heart failure (HF) patients admitted under cardiology and general medicine (GM) without consideration of patients’ frailty.

Aims

To explore outcomes in patients admitted under the two specialities after taking into account their frailty and other characteristics.

Methods

This retrospective study included all HF patients ≥18 years admitted between 1 January 2013 and 31 December 2019 at two Australian tertiary hospitals. Frailty was determined by use of the Hospital Frailty Risk Score (HFRS) and patients with HFRS ≥ 5 were classified as frail. Propensity score matching (PSM) was used to match 11 variables between the two specialities. The primary outcomes included the days-alive-and-out-of-hospital (DAOH90) at 90 days of discharge, 30-day mortality and readmissions.

Results

Of 4913 HF patients, mean age 76.2 (14.1) years, 51% males, 2653 (54%) were admitted under cardiology compared to 2260 (46%) under GM. Patients admitted under GM were more likely to be older females, with a higher Charlson index and poor renal function than those admitted under cardiology. Overall, 23.8% patients were frail and frail patients were more likely to be admitted under GM than cardiology (33.6% vs. 15.3%, P < 0.001). PSM created 1532 well-matched patients in each group. After PSM, the DAOH90 was not significantly different among patients admitted in GM when compared to cardiology (coefficient −5.36, 95% confidence interval −11.73 to 1.01, P = 0.099). Other clinical outcomes were also similar between the two specialities.

Conclusions

Clinical characteristics of HF patients differ between GM and cardiology; however, clinical outcomes were not significantly different after taking into account frailty and other variables.
Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study)
Authors: David Clémence , Duployez Nicolas , Eloy Philippine , Belhadi Drifa , Chezel Julie , Guern Véronique Le , Laouénan Cédric , Fenwarth Laurène , Rouzaud Diane , Mathian Alexis  , de Almeida Chaves Sébastien , Duhaut Pierre , Fain Olivier , Galicier Lionel  , Ghillani-Dalbin Pascale , Kahn Jean Emmanuel , Morel Nathalie , Perard Laurent  , Pha Micheline , Sarrot-Reynauld Francoise , Aumaitre Olivier , Chasset François  , Limal Nicolas , Desmurs-Clavel Helene , Ackermann Felix , Amoura Zahir  , Papo Thomas , Preudhomme Claude , Costedoat-Chalumeau Nathalie , Sacre Karim
Published: February 2022

Objective

The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients—defining clonal haematopoiesis of indeterminate potential (CHIP)—is associated with a predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients.

Methods

The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE.

Results

Screening for CHIP was performed in 438 SLE patients [38 (29–47) years, 91.8% female]. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred >20 years earlier (P < 0.00001) in SLE than in controls. The detection of CHIP at inclusion was not found to be associated with occurrence of CVEs during follow-up [HR = 0.42 (0.06–3.21), P = 0.406].

Conclusion

The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.
‘A Test that is about Your Life’: The Involvement of Refugee Children in Asylum Application Proceedings in the Netherlands
Authors: Rap Stephanie
Published: February 2022

Refugee children are often neither recognised as rights holders nor as active agents in asylum procedures. A one-sided view of these children as vulnerable objects is not in coherence with international children’s rights, including the UN Convention on the Rights of the Child, which regards all children as autonomous subjects and full bearers of rights. Through 21 in-depth interviews with unaccompanied, separated, and accompanied children in the Netherlands, their perceptions and experiences are collected and analysed in relation to their right to be informed and to participate in asylum application proceedings. It is shown that children possess little information on the asylum application interview, which they perceive as particularly stressful. However, they display agency in the choices they make during the interview. Accompanied children find themselves in a rather difficult position, feeling jointly responsible for the outcome of the procedure. It is concluded that effective and meaningful participation, in line with the international children’s rights framework, is difficult to realise in the context of asylum proceedings.
Identification of a Novel ToxA Haplotype of Pyrenophora tritici-repentis from Japan
Authors: Hafez Mohamed , Despins Therese , Nakajima Kaori , Aboukhaddour Reem
Published: February 2022

Pyrenophora tritici-repentis was described first as a pathogen of wheat (tan spot) in Japan in the 1920s, but, since then, no reports on P. tritici-repentis race structure or its effectors in Japan have been published. In this study, 10 single-spore isolates of P. tritici-repentis were collected from bread wheat in Japan. These isolates were evaluated for virulence on four differential wheat genotypes and tested for the presence/absence of the effector-encoding genes, ToxA and ToxB, in multiplex PCR assays. These isolates were identified as ToxA producers, of which eight were designated as race 2 (ToxA producers) and two were classified as race 1 (ToxA and ToxC producers) based on their virulence patterns. Sequence analysis of the ToxA amplicons from these 10 isolates indicated the presence of a novel ToxA haplotype (denoted PtrA2). A comparative sequence analysis and resequencing of ToxA from reference P. tritici-repentis isolates showed that all previously published ToxA haplotypes in P. tritici-repentis were identical, and are hence denoted PtrA1 in this study. A total of 163 PtrToxA sequences from global origins were already deposited in GenBank and were confirmed identical to PtrA1. Sequence variation in PtrA1 and PtrA2 open reading frames were found at three positions: one synonymous mutation at position 412 (C/G) and two nonsynonymous mutations at positions 342 and 362 that alter amino acid sequence. These mutations did not seem to affect the necrosis development on a ToxA-sensitive wheat genotype when rated for symptoms 5 to 7 days after inoculation. This is the first report correctly confirming the presence of an additional novel ToxA haplotype in P. tritici-repentis for which we have predicted its isoform and updated the ToxA haplotype evolutionary network.
Evidence of Coevolution Between Cronartium harknessii Lineages and Their Corresponding Hosts, Lodgepole Pine and Jack Pine
Authors: McAllister Chandra H. , Cullingham Catherine I. , Peery Rhiannon M. , Mbenoun Michael , McPeak Eden , Feau Nicolas , Hamelin Richard C. , Ramsfield Tod D. , Myrholm Colin L. , Cooke Janice E. K.
Published: February 2022

Variation in rate of infection and susceptibility of Pinus spp. to the fungus Cronartium harknessii (syn. Endocronartium harknessii), the causative agent of western gall rust, has been well documented. To test the hypothesis that there is a coevolutionary relationship between C. harknessii and its hosts, we examined genetic structure and virulence of C. harknessii associated with lodgepole pine (P. contorta var. latifolia), jack pine (P. banksiana), and their hybrids. A secondary objective was to improve assessment and diagnosis of infection in hosts. Using 18 microsatellites, we assessed genetic structure of C. harknessii from 90 sites within the ranges of lodgepole pine and jack pine. We identified two lineages (East and West, FST = 0.677) associated with host genetic structure (r = 0.81, P = 0.001), with East comprising three sublineages. In parallel, we conducted a factorial experiment in which lodgepole pine, jack pine, and hybrid seedlings were inoculated with spores from the two primary genetic lineages. With this experiment, we refined the phenotypic categories associated with infection and demonstrated that stem width can be used as a quantitative measure of host response to infection. Overall, each host responded differentially to the fungal lineages, with jack pine exhibiting more resiliency to infection than lodgepole pine and hybrids exhibiting intermediate resiliency. Taken together, the shared genetic structure between fungus and host species, and the differential interaction of the fungal species with the hosts, supports a coevolutionary relationship between host and pathogen.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Merkel Cell Carcinoma, the Impact of Clinical Excision Margins and Mohs Micrographic Surgery on Recurrence and Survival: A Systematic Review
Authors: Uitentuis Sanne E. , Bambach Caroline , Elshot Yannick S. , Limpens Jacqueline , van Akkooi Alexander C. J. , Bekkenk Marcel W.
Published: February 2022

BACKGROUND

When treating Merkel cell carcinoma (MCC), the relation between wide local excision (WLE) margin and recurrence or survival is unclear. Mohs micrographic surgery (MMS) is an alternative surgical option for MCC, but it is unknown whether the local recurrence rate differs between MMS and WLE.

OBJECTIVE

To systematically assess the available literature to determine the recurrence and survival rates when treating MCC with MMS and different clinical excision margins.

MATERIALS AND METHODS

The MEDLINE, EMBASE, and CENTRAL databases were searched. Two independent reviewers selected studies that defined clear excision margins and either recurrence or survival. When possible, individual cases were extracted from case series and included in the analyses. Other studies were reviewed narratively.

RESULTS

Overall, 1108 studies were identified; of which, 19 case series (168 cases) and 12 cohort studies were eligible. None of the cohort studies showed significant differences in recurrence or survival for either excision margins or MMS. Equally, logistic and Cox regression analyses of the case series revealed no significant differences in recurrence or survival between different excision margins and MMS.

CONCLUSION

Synthesis of the available data does not indicate differences in recurrence and/or survival rates for MCC between different clinical excision margins and MMS.
Withholding and withdrawal of life-sustaining therapy in 8569 trauma patients
Authors: Haddam Malik , Kubacsi Laura , Hamada Sophie , Harrois Anatole , James Arthur , Langeron Olivier , Boutonnet Mathieu , Holleville Mathilde , Garrigue Delphine , Leclercq Marion , Hanouz Jean-Luc , Pottecher Julien , Audibert Gérard , Cardinale Mickael , Vinour Hélène , Zieleskiewicz Laurent , Resseguier Noemie , Leone Marc
Published: February 2022

BACKGROUND

This study aimed to determine the prevalence of withholding or withdrawal of life-sustaining therapy (WLST) decisions in trauma ICU patients, using a large registry. We hypothesised that this prevalence is similar to that of the general population admitted to an ICU. As secondary aims, it sought to describe the trauma patients for whom the decision was made for WLST and the factors associated with this decision.

DESIGN

This observational study assessed data from 14 French centres listed in the TraumaBaseTM registry. All trauma patients hospitalised for more than 48 h were pro-spectively included.

RESULTS

Data from 8569 trauma patients, obtained from January 2016 to December 2018, were included in this study. A WLST decision was made in 6% of all cases. In the WLST group, 67% of the patients were older men (age: 62 versus 36, P 
< 0.001); more often they had a prior medical history and higher median severity scores than the patients in the no WLST decision group; SAPS II 58 (46 to 69) versus 21 (13 to 35) and ISS 26 (22 to 24) versus 12 (5 to 22), P 
< 0.001. Neurological status was strongly associated with WLST decisions. The geographic area of the ICUs affected the rate of the WLST decisions. The ICU mortality was 11% (n = 907) of which 47% (n = 422) were preceded by WLST decisions. Fourteen percent of WLST orders were not associated to the death.

CONCLUSION

Among 8569 patients, medical history, trauma severity criteria, notably neurological status and geographical areas were associated with WLST. These regional differences deserve to be investigated in future studies.
Menopausal experiences of South Asian immigrant women: a scoping review
Authors: Zou Ping , Luo Yan , Wyslobicky Melody , Shaikh Haniah , Alam Arzoo , Wang Wei , Zhang Hui
Published: February 2022

Importance and Objective:

South Asians make up a significant portion of global immigration. Immigrants often face challenges when navigating the healthcare system, which can influence their experience during the menopausal transition. The purpose of this scoping review is to summarize the existing literature on South Asian immigrant women's menopausal experience.

Methods:

Various electronic databases were systematically searched to identify research articles. The menopausal experiences of South Asian immigrant women were examined.

Results:

A total of 11 studies were included in this scoping review. A variety of physical symptoms were reported, including vasomotor symptoms, musculoskeletal symptoms, somatic symptoms, and early onset of menopause. Psychosocial symptoms included anxiety, depression, and decreased memory/concentration. Cultural experiences were both positive and negative, depending on the connotations surrounding menopause. Individual facilitators for a healthy transition included education and employment. Familial barriers included a lack of knowledge and support. Community and societal factors were both positive and negative, depending on the level of acculturation. Self-management was the most widely used intervention.

Discussions and Conclusion:

Findings of this scoping review can help guide the development and evaluation of menopause interventions for South Asian immigrant women. Culturally sensitive care, increased discussion on sexual health, support networks, and reduction of socioeconomic barriers are needed to address the health needs of South Asian immigrant women. Further research is needed to better understand South Asian immigrant women's menopausal needs and help guide intervention design.
Association between intergenerational violence exposure and maternal age of menopause
Authors: Foster Holly , Hagan John , Brooks-Gunn Jeanne , Garcia Jess
Published: February 2022

Objective:

To investigate whether maternal violence exposure personally and through her child is associated with an earlier age of menopause, controlling for covariates.

Methods:

Analyses used merged data from two related sources. Although mothers (n = 1,466) were interviewed in 1995 and then 20 years later (2015-17), their children were interviewed in the National Longitudinal Study of Adolescent to Adult Health repeatedly (Waves 1-4, 1994/5 to 2008-2009). Mothers reported their own age of menopause, and mothers and adolescents each reported their own exposure to violence as children and adults.

Results:

A mother's own childhood physical abuse (b = −1.60, P < .05) and her child's sexual abuse (b = −1.39, P < .01) both were associated with an earlier age of menopause. Mothers who were physically abused in childhood and have a child who experienced regular sexual abuse reached menopause 8.78 years earlier than mothers without a history of personal abuse or abuse of their child.

Conclusions:

Our study is the first to find that age of natural menopause is associated with intergenerational violence exposures.
Blood pressure control and glaucoma risk in postmenopausal women: an analysis from the Women's Health Initiative
Authors: Haring Bernhard , Hovey Kathleen , LaMonte Mike , Andrews Chris , Saquib Nazmus , Manson JoAnn E. , Shimbo Daichi , Ritch Robert , De Moraes Carlos Gustavo , Wassertheil-Smoller Sylvia
Published: February 2022

Objective:

Individuals with elevated systolic blood pressure (BP) or low diastolic BP, whether or not on antihypertensive treatment, may be at higher risk for developing glaucoma. We aimed to investigate BP levels in relation to glaucoma risk in a large cohort of postmenopausal women.

Methods:

Prospective follow-up of 101,447 postmenopausal women without prior history of glaucoma enrolled in the Women's Health Initiative Study. BP was measured in-clinic at baseline and after 3 years using standardized procedures. Antihypertensive medication use was determined by drug inventory at baseline and year 3. Women self-reported incident newly diagnosed glaucoma annually. Hazard ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazards analyses adjusting for demographic, medical history, and lifestyle covariates.

Results:

During a mean follow-up of 4.7 years, we documented 7,514 glaucoma cases. Among women not on antihypertensive treatment, those with systolic BP ≥ 140 mm Hg or diastolic BP ≥80 mm Hg were not at higher risk of developing glaucoma (HR 0.97, 95% confidence intervals 0.88-1.08 and HR 1.00 [0.93-1.08], respectively), compared with women with a systolic BP < 120 mm Hg or a diastolic BP 60 to <80 mm Hg. Among women on antihypertensive treatment, neither systolic BP ≥ 140 mm Hg nor diastolic BP ≥80 mm Hg was associated with an increased glaucoma risk (HR 0.89 [0.79-1.00] and HR 0.97 [0.90-1.05], respectively). A diastolic BP <60 mm Hg was not associated with a higher risk compared with a diastolic BP 60 to <80 mm Hg.

Conclusions:

BP control is not associated with an increased or decreased glaucoma risk in postmenopausal women.
Arterial stiffness throughout pregnancy: Arteriograph device-specific reference ranges based on a low-risk population
Authors: Anness Abigail R. , Nath Mintu , Melhuish Kess , Osman Mohammed W. , Webb David , Robinson Thompson , Khalil Asma , Mousa Hatem A.
Published: February 2022

Objective:

The maternal cardiovascular system undergoes significant adaptation during pregnancy. We aimed to examine the changes in arterial stiffness parameters during normal pregnancy and establish reference ranges for the general population.

Methods:

We performed a prospective cross-sectional observational study at the University Hospitals of Leicester. We included low-risk healthy pregnant women with singleton and viable pregnancies with no evidence of foetal abnormality or aneuploidy. Smokers, women with pre-existing or gestational hypertensive disorders and diabetes, booking BMI at least 30, on medication that could affect cardiac function and/or those who delivered before 37 completed weeks of gestation, and/or a neonate with birthweight less than 10th centile were excluded. Brachial (BrAIx) and aortic augmentation indices (AoAIx), and pulse wave velocity (PWV) were assessed using the Arteriograph. Data were analysed using a linear mixed model.

Results:

We analysed a total of 571 readings from 259 women across different gestational ages and present the 10th, 25th, 50th, 75th and 90th centiles for BrAIx, AoAIx and PWV from 12+0 to 42+0 weeks’ gestation. All haemodynamic variables were significantly associated with maternal heart rate. BrAIx, AoAIx and PWV demonstrated significant change with gestation, with all reaching their lowest value in the second trimester.

Conclusion:

The current study presents reference ranges for BrAIx, AoAIx and PWV in low-risk singleton pregnancies. Further work is required to establish if women in whom measures of arterial stiffness lie above the 90th centile could be at increased risk of adverse pregnancy outcomes and to identify the optimum time for screening.
Evaluation of the Effect of Lavender Aroma on Fatigue Among Hemodialysis Patients
Authors: Rahimi Elham , Sedighi Chafjiri Asieh , Hasavari Farideh , Kazem Nezhad Leyli Ehsan , Naseri Maryam , Khosravi Masoud
Published: February 2022

Fatigue is a complication of hemodialysis (HD). We examined the effect of aromatherapy on fatigue in 62 HD patients. Data were collected using a questionnaire and the Piper Fatigue Scale. It was found that fatigue decreased in the intervention group (P < .05). Lavender aromatherapy is useful in reducing fatigue.
Temperature Screening of Healthcare Personnel Is Ineffective in Controlling COVID-19
Authors: Maung Zaw , Kristensen Marissa , Hoffman Bridget , Jacobson Mark A.
Published: February 2022

Objective:

Our aim was to describe the effectiveness of employee temperature screening at a public hospital in San Francisco during the COVID-19 pandemic.

Methods:

An estimated 6000 health care personnel (HCP) underwent daily screening before entry to campus. Logs of failed employee entrance temperature screenings from March 2020 through March 2021 were reviewed.

Results:

From March 2020 through March 2021, only one employee, who reported no symptom that could bar their entry to work, had an elevated temperature on screening. On re-check with an oral thermometer, that individual's temperature was normal.

Conclusions:

While the rationale to continue temperature screening may be rooted in beliefs it will increase employee reporting of symptoms or exposures, our results indicates that such screening of HCP at large US hospitals has no utility in detecting COVID-19 or controlling its transmission.
Healthcare Avoidance in Aircraft Pilots Due to Concern for Aeromedical Certificate Loss
Authors: Hoffman William R. , Aden James , Barbera R. Daniel , Mayes Ryan , Willis Adam , Patel Parth , Tvaryanas Anthony
Published: February 2022

Objective:

To study healthcare avoidance behavior in pilots related to fear of aeromedical certificate loss.

Methods:

Voluntary participation in an anonymous survey distributed to U.S. pilots.

Results:

A total of 3765 pilots were included in the analysis. There were 56.1% of pilots (n = 2111) who reported a history of healthcare avoidance behavior due fear for losing their aeromedical certificate. There were 45.7% who sought informal medical care (n = 1721) and 26.8% who misrepresented/withheld information on a written healthcare questionnaire for fear of aeromedical certificate loss (n = 994).

Conclusions:

Aircraft pilots may participate in healthcare avoidance behavior related to fear of losing their aeromedical certificate. Further work is necessary to address pilot healthcare avoidance.
The indirect impact of heart rate variability on cold pressor pain tolerance and intensity through psychological distress in individuals with chronic pain: the Tromsø Study
Authors: Paccione Charles E. , Bruehl Stephen , My Diep Lien , Rosseland Leiv A. , Stubhaug Audun , Jacobsen Henrik B.
Published: February 2022

Introduction:

Chronic pain (CP) patients often display lower heart rate variability (HRV) and baroreceptor sensitivity (BRS), which are associated with increased evoked pain intensity and decreased pain tolerance.

Objective:

The purpose of this study was to test whether the association between low levels of HRV and BRS and increased evoked pain responsiveness in individuals with CP is mediated by psychological distress and whether this mediation is sex dependent.

Methods:

The sample consisted of 877 participants in Wave 6 of the Tromsø population study who reported clinically meaningful CP. Resting HRV and BRS parameters were derived from continuous beat-to-beat blood pressure recordings. Psychological distress was assessed using the Hopkins Symptom Checklist-10. After cardiovascular assessment, participants completed a 106-second cold pressor task (3°C bath), which assessed cold pressor pain intensity (CPI) and cold pressor pain tolerance (CPT).

Results:

In the full CP sample, mediation analyses showed significant indirect effects, without direct effects, of HRV and BRS on both CPT and CPI via psychological distress. When stratified by sex, significant indirect effects via psychological distress were only found in males for the impact of rMSSD on CPT, the impact of SDNN on CPT, and the impact of BRS on CPT via psychological distress. Moderated mediation analyses revealed that there were no significant sex differences in the indirect effects of HRV and BRS on both CPT and CPI via psychological distress.

Conclusions:

The hypoalgesic impact of cardiovascular regulatory systems on evoked pain responses is conveyed via the indirect effects of psychological distress.
Outcomes after Bone-Ligament-Bone Intercarpal Ligament Reconstruction
Authors: Ross Phillip R. , Gundlach Benjamin , Yue Molin , Chung Kevin C.
Published: February 2022

Background:

Numerous surgical reconstructive techniques have been described for chronic scapholunate and lunotriquetral interosseous ligament instability.

Methods:

The authors retrospectively reviewed 16 consecutive patients who underwent bone-ligament-bone reconstruction for scapholunate or lunotriquetral intraosseous ligament predynamic and dynamic instability at a single tertiary care institution from 2013 to 2019. Clinical and radiographic outcomes, and complications, were recorded.

Results:

Eleven patients had bone-ligament-bone reconstruction for scapholunate ligament injuries and five for lunotriquetral instability. Fourteen patients (87.5 percent) underwent diagnostic arthroscopy before bone-ligament-bone reconstruction, with nine of 14 having grade 3 and four of 14 having grade 4 injury. Capitohamate bone-ligament-bone grafts were used in nine patients (56 percent) and the graft was taken from Lister tubercle in seven (44 percent). The average age at surgery was 37 years. The average follow-up was 60.6 weeks. There were no significant differences between preoperative and postoperative radiographic parameters. Median postoperative wrist flexion was 45 degrees, and mean postoperative wrist extension was 53 degrees, which were significantly less than contralateral flexion (85 degrees; p < 0.0001) and extension (78 degrees; p < 0.0001). Thirty-eight percent of patients complained of persistent pain at final follow-up, and two patients (13 percent) underwent salvage procedures, both at approximately 6.5 months after the index reconstruction.

Conclusion:

Short-term outcomes of bone-ligament-bone reconstruction for early-stage scapholunate and lunotriquetral ligament injuries reveal many patients with residual postoperative wrist pain and disability, and almost uniform limitations in flexion-extension motion.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
A Call for Evidence-Based Conservative Management of Nail Unit Malignancies
Authors: Stiff Katherine M. , Jellinek Nathaniel , Knackstedt Thomas J.
Published: February 2022

Nail unit squamous cell carcinoma and melanoma are the most common malignancies of the nail apparatus. Compared to their cutaneous counterparts, they are diagnosed later and perceived as more aggressive. This may result in overzealous management, including radiographic imaging with poor sensitivity and specificity, interventional nodal staging by sentinel lymph node biopsy, amputation over digit-sparing tumor resections, and elaborate reconstructions after tumor extirpation. In this review article, the authors evaluate the evidence behind several misconceptions in nail malignancy management and provide evidence-based guidance for more conservative care.
Prkra Mutation Alters circRNA Expression During Embryonic External Ear Development
Authors: Liu Wei , Jin Shengyang , Lin Lin , Yang Qinghua , Jiang Haiyue
Published: February 2022

The changes in circRNA expression profile in the mouse external ear tissue during embryonic development to E15.5 and E17.5 can provide clues for the study of the regulation of external ear embryonic development. To understand the changes in gene regulation and expression of circRNA involved in mouse external ear embryonic development, a Prkra Little ear mouse model was used, and the changes in circRNA expression profiles were detected using next-generation sequencing. The changes in the expression of circRNA in the experimental group compared with those in the control group were identified using the find_circ and CiRi2 software, and the differentially expressed circRNAs were annotated via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The results show that the development of mouse external ear embryos is regulated by circRNA expression.
Children with neurodevelopmental disorders: how do they sleep?
Authors: Belli Arianna , Breda Maria , Di Maggio Chiara , Esposito Dario , Marcucci Lavinia , Bruni Oliviero
Published: February 2022

Purpose of review

In this review we summarized the available evidence on sleep disorders in children with neurodevelopmental disorders (NDDs) in particular: intellectual disability (including some genetic conditions such as Prader–Willi Syndrome, Smith-Magenis Syndrome), Autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), Developmental Coordination Disorder, language disorders, and specific learning disorders.

Recent findings

Children with NDDs frequently suffer from sleep disturbances, with a higher prevalence than that of the general pediatric population.

These problems tend to be chronic and may cause additional cognitive and behavioral difficulties, often affecting the whole family's well-being. Sleep behaviors are also related to other important developmental skills, such as attention and listening. Investigating sleep disorders in children with NDDs is therefore crucial in clinical practice. For a systematic approach in clinical practice, we propose the use of a short and easy to remember sleep screening tool.
Role of COVID-19 vaccinal status in admitted children during OMICRON variant circulation in Rio de Janeiro, city- Preliminary report
Authors: Araujo da Silva AR , de Carvalho BRR , Esteves MM , Teixeira CH , Souza CV
Published: February 2022

Objective

To evaluate COVID-19 vaccination status in admitted children during the OMICRON variant circulation.

Design

Observational retrospective study. Patients with confirmed COVID-19 were compared in two different periods: 2020-2021 when full COVID-19 vaccine were not completed for adolescents between 12 and 18 years and 2022, when Pfizer-BioNTech vaccine full scheme were completed for children older 12 years

Setting

Two paediatric hospitals in Rio de Janeiro, city

Patients

Children aged <18 years with confirmed COVID-19.

Intervention

None

Main outcome

Vaccination status for COVID-19 at the admission.

Results

Three-hundred patients were admitted with confirmed COVID-19, being 240 in 2020-2021, and 60 in 2022. The distribution of patients according to the age-groups were: 0-2 years (33.3% in 2020-2021 and 53.4% in 2022), 2-5 years (21.7% in 2020-2021 and 10% in 2022), 5-11 years (29.2% in 2020-2021 and 28.3% in 2022) and 12-18 years (15.8% in 2020-2021 and 8.3% in 2022) (p= 0.015). The median of lenght of stay was 6 days in 2020-2021 and 5 days in 2022 (p=0.036). We verified 6 deaths and in the first period of analysis and 1 death in the second one (p=0.777). Of 60 children admitted in 2022, fifty-eigth (96.7%) not received the full scheme of COVID-19 vaccine available

Conclusions

We verified in a “real world condition” ability of Pfizer-BioNTech vaccine in avoid hospitalization in children older than 12 years
Favipiravir, lopinavir-ritonavir or combination therapy (FLARE): a randomised, double blind, 2x2 factorial placebo-controlled trial of early antiviral therapy in COVID-19
Authors: Lowe David M , Brown Li-An K , Chowdhury Kashfia , Davey Stephanie , Yee Philip , Ikeji Felicia , Ndoutoumou Amalia , Shah Divya , Lennon Alexander , Rai Abhulya , Agyeman Akosua A , Checkley Anna , Longley Nicola , Dehbi Hakim-Moulay , Freemantle Nick , Breuer Judith , Standing Joseph F ,   FLARE Investigators
Published: February 2022

Background

Early antiviral treatment is effective for COVID-19 but currently available agents are expensive. Favipiravir is routinely used in many countries, but efficacy is unproven. Antiviral combinations have not been systematically studied. We aimed to evaluate the effect of favipiravir, lopinavir-ritonavir or the combination of both agents on SARS-CoV-2 viral load trajectory when administered early.

Methods

We conducted a Phase 2, proof of principle, randomised, placebo-controlled, 2×2 factorial, double-blind trial of outpatients with early COVID-19 (within 7 days of symptom onset) at two sites in the United Kingdom. Participants were randomised using a centralised online process to receive: favipiravir (1800mg twice daily on Day 1 followed by 400mg four times daily on Days 2-7) plus lopinavir-ritonavir (400mg/100mg twice daily on Day 1, followed by 200mg/50mg four times daily on Days 2-7); favipiravir plus lopinavir-ritonavir placebo; lopinavir-ritonavir plus favipiravir placebo; or both placebos. The primary outcome was SARS-CoV-2 viral load at Day 5, accounting for baseline viral load. ClinicalTrials·gov: NCT04499677.

Findings

Between 6 October 2020 and 4 November 2021, we recruited 240 participants. For the favipiravir+lopinavir-ritonavir, favipiravir+placebo, lopinavir-ritonavir+placebo and placebo-only arms, we recruited 61, 59, 60 and 60 participants and analysed 55, 56, 55 and 58 participants respectively who provided viral load measures at Day 1 and Day 5. In the primary analysis, the mean viral load in the favipiravir+placebo arm had decreased by 0.57 log10 (95% CI -1.21 to 0.07, p=0.08) and in the lopinavir-ritonavir+placebo arm by 0.18 log10 (95% CI -0.82 to 0.46, p=0.58) more than in the placebo arm at Day 5. There was no significant interaction between favipiravir and lopinavir-ritonavir (interaction coefficient term: 0.59 log10, 95% CI -0.32 to 1.50, p=0.20). More participants had undetectable virus at Day 5 in the favipiravir+placebo arm compared to placebo only (46.3% vs 26.9%, odds ratio (OR): 2.47, 95% CI 1.08 to 5.65; p=0.03). Adverse events were observed more frequently with lopinavir-ritonavir, mainly gastrointestinal disturbance. Favipiravir drug levels were lower in the combination arm than the favipiravir monotherapy arm.

Interpretation

At the current doses, no treatment significantly reduced viral load in the primary analysis. Favipiravir requires further evaluation with consideration of dose escalation. Lopinavir-ritonavir administration was associated with lower plasma favipiravir concentrations.

Funding

LifeArc, UK.
Co-infection with SARS-COV-2 Omicron and Delta Variants Revealed by Genomic Surveillance
Authors: Rockett Rebecca J , Draper Jenny , Gall Mailie , Sim Eby M , Arnott Alicia , Agius Jessica E , Johnson-Mackinnon Jessica , Martinez Elena , Drew Alexander P , Lee Clement , Ngo Christine , Ramsperger Marc , Ginn Andrew N , Wang Qinning , Fennell Michael , Ko Danny , Huston Linda , Kairaitis Lukas , Holmes Edward C , O’Sullivan Matthew N , Chen Sharon C-A , Kok Jen , Dwyer Dominic E , Sintchenko Vitali
Published: February 2022

We identified the co-infection of the SARS-CoV-2 Omicron and Delta variants in two epidemiologically unrelated patients with chronic kidney disease requiring haemodialysis. Both SARS-CoV-2 variants were co-circulating locally at the time of detection. Amplicon- and probe-based sequencing using short- and long-read technologies identified and quantified Omicron and Delta subpopulations in respiratory samples from the two patients. These findings highlight the importance of genomic surveillance in vulnerable populations.
Genome Enrichment of Rare, Unknown Species from Complicated Microbiome by Nanopore Selective Sequencing
Authors: Sun Yuhong , Li Xiang , Yang Qing , Zhao Bixi , Wu Ziqi , Xia Yu
Published: February 2022

Rare species are vital members of a microbial community, but retrieving their genomes is difficult due to their low abundance. The ReadUntil (RU) approach allows nanopore devices to sequence specific DNA molecules selectively in real-time, which provides an opportunity for enriching rare species. However, there is still a gap in RU-based enriching of rare and unknown species in environmental samples whose community composition is unclear, and many species lack corresponding reference in public databases. Here we present metaRUpore to overcome this challenge. We applied metaRUpore to a thermophilic anaerobic digester (TAD) community, it successfully redirected the sequencing throughput from high-abundance populations to rare species while facilitating the recovery of 41 high-quality metagenome-assembled genomes (MAGs) at low sequencing effort. The simplicity and robustness of the approach make it accessible for labs with moderate computational resources and hold the potential to become the standard practice in future metagenomic sequencing of complicated microbiomes.
KIBRA Regulates AMPA Receptor Expression, Synaptic Plasticity, and Memory in an Age-Dependent Manner
Authors: Mendoza Matthew L. , Quigley Lilyana , Dunham Thomas , Volk Lenora J.
Published: February 2022

The biological mechanisms supporting age-dependent changes in learning and memory remain elusive. While a growing body of human literature implicates KIBRA in memory and neurodevelopmental disorders, KIBRA’s molecular function and contribution to maturation of synaptic function and cognition remain poorly understood. Despite being expressed throughout early postnatal development, germline deletion of KIBRA impairs synaptic plasticity selectively in adult rodents. However, it is unclear whether KIBRA facilitates proper brain maturation necessary for adult plasticity or whether it plays a distinct role in plasticity in the adult brain. Here, using an inducible KIBRA knockout mouse, we demonstrate that acutely deleting KIBRA in adult forebrain neurons impairs both spatial memory and long-term potentiation (LTP). The deficits in LTP correlate with an adult-selective decrease in extrasynaptic AMPA receptors under basal conditions. We also identify a novel role for KIBRA in LTP-induced AMPAR upregulation. In contrast, acute deletion of KIBRA in juvenile forebrain neurons did not affect LTP and had minimal effects on basal AMPAR expression. These data suggest that KIBRA serves a unique role in adult hippocampal function through regulation of basal and activity-dependent AMPAR proteostasis that supports synaptic plasticity.

Significance Statement

Synaptic plasticity supported by trafficking of postsynaptic AMPA receptors is a conserved mechanism underlying learning and memory. The nature and efficacy of learning and memory undergo substantial changes during childhood and adolescent development, but the mechanisms underlying this cognitive maturation remain poorly understood. Here, we demonstrate that the human memory- and neurodevelopmental disorder-associated gene KIBRA facilitates memory and hippocampal synaptic plasticity selectively in the adult hippocampus. Furthermore, we show that selective loss of KIBRA from adult but not juvenile neurons reduces expression of extrasynaptic AMPA receptors and prevents LTP-induced increases in AMPAR expression. Overall, our results suggest that KIBRA participates in cellular and molecular processes that become uniquely necessary for memory and synaptic plasticity in early adulthood.
Clinical and immunological features of SARS-CoV-2 breakthrough infections in vaccinated individuals requiring hospitalization
Authors: Lamacchia Giulia , Mazzoni Alessio , Spinicci Michele , Vanni Anna , Salvati Lorenzo , Peruzzi Benedetta , Bencini Sara , Capone Manuela , Carnasciali Alberto , Farahvachi Parham , Rocca Arianna , Kiros Seble Tekle , Graziani Lucia , Zammarchi Lorenzo , Mencarini Jessica , Colao Maria Grazia , Caporale Roberto , Liotta Francesco , Cosmi Lorenzo , Rossolini Gian Maria , Bartoloni Alessandro , Maggi Laura , Annunziato Francesco
Published: February 2022

Background

Waning immunity and the surge of SARS-CoV-2 variants are responsible for breakthrough infections, i.e. infections in fully vaccinated individuals. Although the majority of vaccinated infected subjects reports mild or no symptoms, some others require hospitalization. The clinical and immunological features of vaccinated hospitalized COVID-19 patients are currently unknown.

Methods

29 unvaccinated and 36 vaccinated hospitalized COVID-19 patients were prospectively enrolled and clinical and laboratory data. Immunophenotyping of leukocytes’ subsets, T and B cell SARS-CoV-2 specific responses were evaluated via flow cytometry. Anti-IFN-α autoantibodies were measured via ELISA.

Results

Despite vaccinated patients were older and with more comorbidities, unvaccinated subjects showed higher levels of pro-inflammatory markers, more severe disease and increased mortality rate. Accordingly, they presented significant alterations in the circulating leukocyte composition, typical of severe COVID-19. Vaccinated patients displayed higher levels of anti-Spike IgGs and Spike-specific B cells. Of all participants, survivors showed higher levels of anti-Spike IgGs and S-specific CD4+ T cells than non-survivors. At hospital admission, 6 out of 65 patients (9.2%) displayed high serum concentrations of autoantibodies targeting IFN-α. Remarkably, 3 were unvaccinated and eventually died, while the other 3 were vaccinated and survived.

Conclusion

Despite more severe pre-existing clinical conditions, vaccinated patients have good outcome. A rapid activation of anti-SARS-CoV-2-specific immunity is fundamental for the resolution of the infection. Therefore, prior immunization through vaccination provides a significant contribute to prevention of disease worsening and can even overcome the presence of high-risk factors (i.e. older age, comorbidities, anti-IFN-α autoantibodies positivity).
Increased Potency and Breadth of SARS-CoV-2 Neutralizing Antibodies After a Third mRNA Vaccine Dose
Authors: Muecksch Frauke , Wang Zijun , Cho Alice , Gaebler Christian , Tanfous Tarek Ben , DaSilva Justin , Bednarski Eva , Ramos Victor , Zong Shuai , Johnson Brianna , Raspe Raphael , Schaefer-Babajew Dennis , Shimeliovich Irina , Daga Mridushi , Yao Kai-Hui , Schmidt Fabian , Millard Katrina G. , Turroja Martina , Jankovic Mila , Oliveria Thiago Y. , Gazumyan Anna , Caskey Marina , Hatziioannou Theodora , Bieniasz Paul D. , Nussenzweig Michel C.
Published: February 2022

The omicron variant of SARS-CoV-2 infected very large numbers of SARS-CoV-2 vaccinated and convalescent individuals1–3. The penetrance of this variant in the antigen experienced human population can be explained in part by the relatively low levels of plasma neutralizing activity against Omicron in people who were infected or vaccinated with the original Wuhan-Hu-1 strain4–7. The 3rd mRNA vaccine dose produces an initial increase in circulating anti-Omicron neutralizing antibodies, but titers remain 10-20-fold lower than against Wuhan-Hu-1 and are, in many cases, insufficient to prevent infection7. Despite the reduced protection from infection, individuals that received 3 doses of an mRNA vaccine were highly protected from the more serious consequences of infection8. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving 3 mRNA vaccine doses9,10. We find that the 3rd dose is accompanied by an increase in, and evolution of, anti-receptor binding domain specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the 2nd vaccine dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared to antibodies obtained after the 2nd vaccine dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells that differed from the persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analyzed neutralizing antibodies in the memory compartment obtained from individuals receiving a 3rd mRNA vaccine dose neutralized Omicron. Thus, individuals receiving 3 doses of an mRNA vaccine encoding Wuhan-Hu-1, have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help explain why a 3rd dose of an mRNA vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.
Remodeling of human colon plasma cell repertoire in ulcerative colitis
Authors: Scheid Johannes F. , Eraslan Basak , Hudak Andrew , Brown Eric , Sergio Dallis , Delorey Toni , Phillips Devan , Lefkovith Ariel , Jess Alison T. , Duck Lennard W. , Elson Charles O. , Vlamakis Hera , Deguine Jacques , Ananthakrishnan Ashwin , Graham Daniel B. , Regev Aviv , Xavier Ramnik J.
Published: February 2022

Plasma cells (PCs) constitute a significant fraction of cells in colonic mucosa and contribute to inflammatory lymphocytic infiltrates in ulcerative colitis (UC). While gut PCs secrete 3-5 g of immunoglobulins daily, including IgA antibodies that target colitogenic bacteria, their role in UC is not known. Here, we combined B cell sorting with single-cell VDJ- and RNA-seq and monoclonal antibody (mAb) testing to characterize the colonic PC repertoire in healthy individuals and patients with UC. We show that a large fraction of B cell clones is shared between different colon regions and that inflammation in UC disrupts this landscape, causing clonal expansion and isotype skewing from IgA1 and IgA2 to IgG1. mAbs produced from expanded PC clones show low polyreactivity and autoreactivity and target specific bacterial strains. Expression profiles of individual PCs from inflamed and non-inflamed colon regions indicate that inflammation is associated with up-regulation of the unfolded protein response (UPR) and antigen presentation genes. Together, our results characterize the microbiome-specific PC response in the colon, its disruption in UC and how PCs might contribute to inflammation in UC.