bluuebunny/crossref_metadata_2025 huggingface dataset:
PREDICTORS OF RETINAL PIGMENT EPITHELIUM TEAR DEVELOPMENT AFTER TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Yasuhara Satoshi , Miyata Manabu , Ooto Sotaro , Tamura Hiroshi , Ueda-Arakawa Naoko , Uji Akihito , Muraoka Yuki , Miyake Masahiro , Takahashi Ayako , Wakazono Tomotaka , Yamashiro Kenji , Tsujikawa Akitaka
Published: February 2022

Purpose:

The purpose of this study was to investigate the predictors of retinal pigment epithelium (RPE) tear development after treatment for neovascular age-related macular degeneration using swept source optical coherence tomography angiography.

Methods:

This prospective study included 152 treatment-naïve eyes with neovascular age-related macular degeneration without high myopia that were followed up for 1 year after treatment. Eligible eyes were classified into eyes with or without RPE tear development. They were matched in a 1:2 ratio. The areas of choroidal neovascularization (CNV) and RPE detachment (pigment epithelial detachment [PED]) were measured from optical coherence tomography angiography and OCT en face images, respectively. The optical coherence tomography angiography–specific parameters representing CNV status were analyzed.

Results:

Eight (5.3%) of the 152 eyes developed RPE tears (RPE tear group). After matching, 16 eyes without RPE tears were analyzed (non-RPE tear group). The ratio of the CNV/PED area was lower in the RPE tear group than that in the non-RPE tear group (P = 0.007). The PED area was broader (P = 0.008), and PED height was greater in the RPE tear group (P = 0.04). Optical coherence tomography angiography–specific parameters did not differ between the two groups.

Conclusion:

Neovascular age-related macular degeneration with pretreatment broad PED, high PED, and small CNV area relative to the PED area has a high risk of RPE tear development after therapy. However, CNV status may not have an association.
ENDOGENOUS ENDOPHTHALMITIS DUE TO STREPTOCOCCUS ANGINOSUS IN A HEALTHY, YOUNG WOMAN
Authors: Lin Jonathan B. , Eliott Dean , Sobrin Lucia , Stryjewski Tomasz P.
Published: February 2022

Purpose:

The purpose of this study was to present a case of indolent endogenous endophthalmitis in a young, seemingly healthy woman.

Methods:

This study is a retrospective case report.

Results:

A 25-year-old woman with no significant medical history presented with vision loss in the left eye over the course of 1 month. Examination showed vitritis and a white–yellow lesion overlying the macula and optic nerve in the left eye. Initial laboratory testing for infectious and inflammatory causes was unrevealing. A diagnostic vitrectomy was performed, and the patient was found to have presumed endogenous endophthalmitis due to Streptococcus anginosus, an extremely uncommon bacterium. Subsequent workup did not reveal evidence of bacteremia, endocarditis, or orbital infection. This case is unique because, unlike the three previously reported cases of S. anginosus endophthalmitis, this patient was seemingly healthy, never had an elevated white blood cell count, never had documented bacteremia, had a normal echocardiogram, and had normal orbital findings on magnetic resonance imaging and computed tomography scans. Further questioning revealed a remote history of facial cellulitis and possible sinusitis treated with oral antibiotics, which are the presumed etiology.

Conclusion:

Streptococcus anginosus endophthalmitis can occur in young, seemingly healthy patients. Endogenous endophthalmitis should be considered in the differential diagnosis even without systemic comorbidities or other risk factors. Detailed questioning about medical history and thorough review of systems, including nonocular symptoms, are essential.
VOGT–KOYANAGI–HARADA DISEASE-LIKE UVEITIS IN A PATIENT WITH ADVANCED MELANOMA TREATED BY SEQUENTIAL ADMINISTRATION OF NIVOLUMAB AND DABRAFENIB/TRAMETINIB THERAPY
Authors: Madoe Aline , Schauwvlieghe Pieter-Paul , Jacob Julie
Published: February 2022

Purpose:

To describe a case of bilateral Vogt–Koyanagi–Harada (VKH)-like uveitis during treatment with dabrafenib and trametinib and three months after discontinuation of nivolumab for malignant melanoma, and discuss the possible (synergistic) role(s) of mitogen-activated protein kinase (MAPK) inhibitors and immune checkpoint inhibitors in its pathophysiology.

Methods:

Retrospective case report with fluorescein angiography and optical coherence tomography.

Results:

A 55-year old patient with metastatic melanoma presented with a complaint of gradually worsening blurry vision in the right eye during treatment with dabrafenib and trametinib, three months after discontinuation of nivolumab. Based on the clinical examination, optical coherence tomography and fluorescein angiography findings, and a thorough laboratory work-up, he was diagnosed with a bilateral VKH-like uveitis without extraocular manifestations. The uveitis responded well to oral corticosteroids.

Conclusion:

Vogt–Koyanagi–Harada-like uveitis is a rare adverse effect of MAPK inhibitors and immune checkpoint inhibitors. Similar pathogenetic mechanisms including a drug-induced autoimmunity targeted against benign and malignant melanocytes may underlie MAPK inhibitor-induced and immune checkpoint inhibitors-induced VKH-like uveitis. In our report, the patient developed a VKH-like uveitis during MAPK inhibition therapy, four months after discontinuation of nivolumab. It is difficult to delineate whether MAPK inhibition alone was responsible for this adverse effect, or whether, on the contrary, potentiation occurred as a result of immune modulation by previous treatment with an immune checkpoint inhibitor. Further cases are needed to further clarify this latter hypothesis.
SPONTANEOUS FORMATION AND RESOLUTION OF A LAMELLAR HOLE IN A PATIENT SUCCESSFULLY TREATED FOR DIABETIC MACULAR EDEMA WITH A FLUOCINOLONE ACETONIDE IMPLANT
Authors: Shah Saumya M. , Bakri Sophie J.
Published: February 2022

Purpose:

The purpose of this study was to report a case of spontaneous formation and resolution of a lamellar macular hole in a patient with diabetic macular edema treated with steroid implants.

Methods:

This study is a case report.

Results:

A 53-year-old man presented with blurry vision and was found to have diabetic macular edema that remained refractory to treatment despite multiple short-term intravitreal steroid implants. He was eventually treated with an intravitreal fluocinolone acetonide implant and was subsequently noted to have developed a lamellar macular hole that then resolved spontaneously without any additional therapy.

Conclusion:

There can be spontaneous formation and resolution of lamellar holes in the treatment of diabetic macular edema because of reorganization of the inner retinal layers, without significant impact on visual acuity. To the best of our knowledge, this finding has not been previously reported.
Bacterial and Fungal Gut Dysbiosis and Clostridium difficile in COVID-19
Authors: Linares-García Laura , Cárdenas-Barragán María E. , Hernández-Ceballos Winston , Pérez-Solano Carlos S. , Morales-Guzmán Alizon S. , Miller Danielle S. , Schmulson Max
Published: February 2022

Background:

Gastrointestinal symptoms are common in Coronavirus Disease 2019 (COVID-19), related to infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) of intestinal cells through the angiotensin converting enzyme 2 (ACE2) receptor in the brush border. Also, patients are treated with multiple antibiotics. Therefore, an increase in gut dysbiosis and in the prevalence of Clostridium difficile infection (CDI) is expected in patients with COVID-19.

Methods:

A PubMed search was conducted using the terms “gut microbiota,” “gut mycobiota,” “dysbiosis” AND “COVID-19”; “Clostridium difficile,” “Clostridioides difficile” AND “COVID-19”; “probiotics,” “bacteriotherapy AND COVID-19.” Only case series, observational and experimental studies were included.

Results:

A total of 384 papers were retrieved and 21 fulfilled selection criteria. Later, a new paper was identified, thus 22 papers were reviewed. Main findings: (1) gut bacterial dysbiosis has been found in fecal samples of COVID-19 patients, with enrichment of opportunistic organisms and decrease of beneficial commensals such as Faecalibacterium prausnitizii. Dysbiosis is related to inflammatory markers and illness severity. (2) There is evidence for abnormal gut barrier and bacterial translocation with a negative impact in the lungs. (3) Fungal dysbiosis correlating with pulmonary mycobiota, has also been found. (4) There is controversy in the CDI rates among COVID-19 patients versus controls and pandemic versus prepandemic era. (5) There is no available evidence yet to support bacteriotherapy in COVID-19. (6) Fecal microbiota transplantation (FMT) has been proposed for COVID-19, although there is no evidence to support it. Also, FMT can be safely used during the pandemic for CDI if strict screening protocols for donors and fecal product are implemented.

Conclusions:

In COVID-19 there is bacterial and fungal dysbiosis that correlates with systemic and pulmonary inflammation, and illness severity. Further investigations are warranted to determine the efficacy of bacteriotherapy and FMT for modulating gut dysbiosis in COVID-19.
Recognizing vitamin A deficiency: special considerations in low-prevalence areas
Authors: Song Ailin , Mousa Hazem M. , Soifer Matias , Perez Victor L.
Published: February 2022

Purpose of review

Although vitamin A deficiency (VAD) is rare in well resourced countries, there is a growing trend of VAD in at-risk pediatric populations. Early diagnosis is critically important to prevent its associated morbidity and mortality. This review highlights key lessons for evaluation, diagnosis, and management of children with xerophthalmia in the United States. It synthesizes the latest findings from the literature on the pathophysiology, epidemiology, risk factors, evaluation, and management of VAD in low-prevalence areas.

Recent findings

Vitamin A is crucial for maintaining the functional integrity of the eye, immune system, skin, and mucous membranes. Despite the scarcity of VAD in developed countries, there are increasing reports of VAD in at-risk children, including those with autism spectrum disorder and gastrointestinal conditions. There is a broad range of manifestations of VAD, posing a diagnostic challenge. Familiarity with the variable presentations of VAD and having a high index of suspicion in at-risk populations can aid in its early diagnosis. Systemic vitamin A supplementation and a multidisciplinary approach are important components of the management of VAD.

Even in well resourced countries, VAD should remain on the differential in patients with risk factors who present with relevant signs and symptoms. Early diagnosis and appropriate involvement of a multidisciplinary care team can help prevent morbidity and mortality associated with VAD.
Advantages of Proactive Therapeutic Drug Monitoring in a Prospective Cohort of Children With Inflammatory Bowel Disease Treated With Anti‐Tumour Necrosis Factor
Authors: Gasparetto Marco , Burgess Natasha , Naik Sandhia , Studart Dominic , Kadir Ahmed , Croft Nick , Sanderson Ian , Deb Protima
Published: February 2022

Few studies have addressed whether proactive therapeutic drug monitoring (TDM) results in improved clinical outcomes in children with inflammatory bowel disease (IBD) treated with anti‐tumour necrosis factor. The aim of this study was to investigate the impact of using proactive TDM in this patient group.

Pilot single‐centre observational study to accrue data on patients managed with proactive TDM.

More patients in the proactive TDM cohort were managed by escalating the infliximab (IFX) regime (P < 0.001). The need for switching to different biologics was significantly lower in this patient group (P < 0.001).

The introduction of proactive TDM resulted in a significant reduction of patients requiring switch of their primary biologic. The results of this study are indicators that proactive TDM offers a better method of managing children with IBD on IFX therapy.
The Utility of Functional Luminal Imaging Probes Measurements to Diagnose Dysmotility and Their Relationship to Impaired Bolus Clearance
Authors: Rosen Rachel , Stayn Zachary , Garza Jose M. , DiFilippo Courtney , Cohen Alexandra , Kane Madeline , Wall Stephanie , Nurko Samuel
Published: February 2022

Background:

Functional luminal imaging probes (FLIP) have been used by multiple centers to assess esophagogastric junction (EGJ) function in patients at risk for esophageal obstruction but its role in diagnosing peristaltic disorders is less well studied. In particular, there are no studies comparing the sensitivity of FLIP to diagnose motility abnormalities and impaired bolus transit by high‐resolution esophageal manometry with impedance.

Methods:

We prospectively recruited 42 patients undergoing high‐resolution esophageal manometry with impedance (HRIM) who also underwent FLIP between 2018 and 2020. HRIM parameters were analyzed using Swallow Gateway software to determine peristaltic and lower esophageal sphincter pressure measurements as well as bolus flow parameters. FLIP tracings were analyzed for the presence of repetitive antegrade contractions (RACs), EGJ distensibility, and associated parameters.

Results:

Forty‐two patients were included (11 controls, 7 achalasia, 16 fundoplication, 8 dysmotility). The mean age of patients was 10.1 ± 0.9 years. There were significant differences in bolus flow parameters across diagnosis with longer bolus presence (BPT) in control patients compared with fundoplication and dysmotility patients. There was a significant correlation between EGJ diameter, EGJ distensibility and bolus flow time (BFT) for solid foods (r2 > 0.518, P < 0.02). The presence of RACs and EGJ relaxation during RACs was associated with a greater BFT and BPT across textures (P < 0.05). Forty‐two percentage of patients with absent RACs, however, had clear peristalsis by HRIM.

Conclusions:

The presence of RACs and EGJ relaxation by FLIP correlate with improved bolus flow. Patients with an absence of RACs need HRIM to confirm any diagnoses of dysmotility.
Case Report of a Massive Life-threatening Neonatal Thrombosis Treated With a Targeted, Goal-oriented Scheme of Urokinase
Authors: Rossi Alessandra , Ciarmoli Elena , Villani Paolo , Saldi Gabriele , Pierro Maria
Published: February 2022

Background:

Thrombotic events are severe, often under-diagnosed, complications occurring in newborn infants during their hospital stay. Currently, there is no consensus regarding the optimal treatment scheme for thrombolysis in neonates.

Observations:

We present the case of a newborn suffering from a life-threatening thrombosis. Diagnosis was suggested by a gradual increase of C-reactive protein, with repeatedly normal procalcitonin. Thrombosis was successfully and safely treated with a long scheme of 21 days of urokinase, supported by vascular ultrasound and d-dimer trend.

Conclusions:

Laboratory and ultrasound results may help in adjusting the duration of the thrombolytic treatment, allowing for longer therapeutic schemes that could optimize treatment success. In addition, our case may suggest a possible combined role of C-reactive protein and procalcitonin as an early diagnostic aid in neonatal thrombosis.
Extrarenal Anaplastic Wilms Tumor: A Case Report With Genomic Analysis and Tumor Models
Authors: Willis Kelsi R. , Sathe Adwait A. , Xing Chao , Koduru Prasad , Artunduaga Maddy , Butler Erin B. , Park Jason Y. , Kurmasheva Raushan T. , Houghton Peter J. , Chen Kenneth S. , Rakheja Dinesh
Published: February 2022

Primary extrarenal Wilms tumors are rare neoplasms that are presumed to arise from metanephric or mesonephric remnants outside of the kidney. Their pathogenesis is debated but has not been studied, and there are no reports of genomic descriptions of extrarenal Wilms tumors. We describe a diffusely anaplastic extrarenal Wilms tumor that occurred in the lower abdomen and upper pelvis of a 10-year-old boy. In addition to the clinical, histopathologic, and radiologic features, we describe the cytogenetic changes and exomic profile of the tumor. The tumor showed loss of the tumor suppressor AMER1, loss of chromosome regions 1p, 16q, and 22q, gain of chromosome 8, and loss of function TP53 mutation—findings known to occur in renal Wilms tumors. This is the first description of the exomic profile of a primary extrarenal Wilms tumor. Our data indicate that primary extrarenal Wilms tumors may follow the same pathogenetic pathways that are seen in renal Wilms tumors. Finally, we describe the establishment of first ever tumor models (primary cell line and patient-derived xenograft) from an extrarenal Wilms tumor.
Predictive Value of Breg and Serum IL-10 Concentration Levels for Acute ITP Progression to Chronic Phase
Authors: Aref Salah , El Menshawy Nadia , Darwish Ahmad , Farag Nora A.
Published: February 2022

Introduction:

Pediatric immune thrombocytopenia (ITP) is a potentially life threating autoimmune disorder with different responses to therapy and different bleeding phenotypes in critical organs. The molecular basis for the variable response has not yet been fully elucidated. This study was designed to address the predictive value of regulatory B-cell (Breg) count and interleukin-10 (IL-10) serum levels for acute ITP patients who progress to chronic phase. The present study included 80 children with acute ITP )38 males and 42 females (with median age of 8 years and 40 matched healthy controls. Assessment of Breg (CD19+CD24hiCD38hi) was carried out by a multicolor flowcytometry, however, IL-10 serum levels were evaluated by enzyme-linked immunosorbent assay. A significant reduction of Breg percentage and a significant increase in serum IL-10 levels were identified in children with acute ITP as compared with controls (P<0.001 for both). Fourteen ITP patients passed to chronic phase, while 66 patients achieved remission within 6 months. The absolute Breg was significantly lower, while IL-10 was significantly higher in patients with acute ITP who progressed to chronic phase in comparison with acute ITP patients who achieved complete remission. Cox proportional hazards for ITP chronicity revealed that IL-10 OR was 2.46 (confidence interval: 1.42-4.27; P=0.001) and absolute Breg OR was 0.147 (confidence interval: 0.128-0.624; P=0.005) in the peripheral blood. Therefore, they could predict chronicity in ITP cases.

Conclusion:

Reduced Breg count and elevated IL-10 levels in patients with acute ITP at diagnosis can predict chronicity.
Health Workers’ Perception and Emotions Surrounding Teleconsultation in Pediatric Cancer Care During the COVID-19 Pandemic
Authors: Calò Pierluigi , Leblond Pierre , Girodet Magali , Gauchet Alice , Anota Amélie , Christophe Veronique , Bertrand Amandine
Published: February 2022

Background and Aims:

During the first lockdown of the coronavirus disease 2019 (COVID-19) pandemic, we developed a teleconsultation model and conducted a survey-based study with the aim to evaluate satisfaction and emotions of health workers (HWs), to assess the feasibility of teleconsultations, and to evaluate technical issues.

Materials and Methods:

This is a prospective monocentric exploratory study based on synchronous, video consultations between HWs and pediatric patients treated for blood or solid malignancies or blood benign diseases. Every HW completed an online survey which covered technical aspects, data concerning satisfaction, quality of the interaction with the patient, and emotions felt after the teleconsultation. A score was calculated for each aspect.

Results:

Eleven specialists participated in the study, and we selected 84 questionnaires. With a satisfaction rate of 74%, HWs felt mostly calm (80%), relaxed (70%), stress-free (69%), and relieved (65%). We calculated the following median scores: an overall satisfaction score of 6.67 (0 to 10), a global feeling score of 8.79 (3.33 to 10.00), and a quality score of 7.34 (2.50 to 10.00). A strong correlation between the quality of teleconsultation and the satisfaction of the HWs has been highlighted (r=0.588).

Conclusion:

Our series is an encouragingly positive experience from the perspective of the HWs, their feelings, and perceptions.
Clinicopathologic Evaluation and Molecular Profiling of Recurrent Stage IA Endometrial Endometrioid Carcinoma: A Case-control Study
Authors: Sharma Aarti E. , Moran Angelica , Somasegar Sahana , Steinhardt George , Chapel David B. , Lastra Ricardo R. , Lee Nita K. , Ritterhouse Lauren L. , Bennett Jennifer A.
Published: February 2022

Most low-grade, early-stage endometrial endometrioid carcinomas (EEC) have an excellent prognosis; however, recurrences occur in a small subset with several studies reporting an increase in CTNNB1 exon 3 mutations in this population. Herein we evaluated 10 recurrent low-grade (FIGO 1 or 2), early-stage (FIGO IA) EECs matched to 10 nonrecurrent EECs to further characterize their clinicopathologic features and molecular phenotype. Cases were matched to controls based on size, grade, and depth of invasion. All tumors were evaluated for specific clinicopathologic parameters followed by next-generation sequencing using a 1213 gene panel. Recurrent EECs demonstrated no significant clinicopathologic differences when compared with nonrecurrent EECs, in terms of age, body mass index, pattern of invasion, presence of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia, associated metaplastic changes, peritumoral lymphocytes, mitoses, and tumor-infiltrating lymphocytes. Both cohorts also showed a similar number of pathogenic mutations, including CTNNB1 exon 3 mutations, as well as tumor mutational burden and microsatellite profiles. Although in this particular study, the lack of correlation between CTNNB1 exon 3 mutation and recurrence might be secondary to a small sample size, it also suggests the presence of other contributing factors. Thus, it helps set the foundation for larger series incorporating whole genome, transcriptome, proteome, and epigenome analyses to answer this clinically important question.
Relationship of Subcutaneous Adipose Tissue Inflammation–Related Gene Expression With Ectopic Lipid Deposition in Persons With HIV
Authors: Bailin Samuel S. , Gabriel Curtis L. , Fan Run , Ye Fei , Nair Sangeeta , Terry James G. , Carr John J. , Silver Heidi , Wanjalla Celestine N. , Mashayekhi Mona , Lima Morgan , Woodward Beverly , Hannah LaToya , Fuseini Hubaida , Ferguson Jane F. , Kropski Jonathan A. , Koethe John R.
Published: February 2022

Objective:

Fat redistribution from subcutaneous adipose tissue (SAT) to the abdominal viscera, pericardium, liver, and skeletal muscle contributes to the rising burden of cardiometabolic disease among persons with HIV (PWH). Previous studies found SAT inflammation in PWH impairs lipid storage and persists despite plasma viral suppression on antiretroviral therapy (ART). In this study, we identified SAT immune-related genes associated with ectopic fat deposition in PWH on long-term ART.

Design and methods:

A total of 92 PWH with well-controlled viremia underwent computed tomography imaging and abdominal SAT biopsy for gene expression analysis. SAT gene expression was measured using a NanoString panel of 255 immune-related genes. Associations between gene expression and computed tomography measurements of the volume and attenuation (radiodensity) of metabolically relevant ectopic fat depots were assessed using multivariable linear regression and network analysis.

Results:

Greater SAT volume was associated with higher visceral and pericardial adipose tissue volume, but lower skeletal muscle attenuation. Lower SAT attenuation, a measure of lipid content, was associated with lower visceral adipose tissue attenuation. Hierarchical clustering identified a subset of macrophage-related genes in SAT, includingCCL2,CCL22,CCL13,CCR1,CD86,CD163,IL-6,IL-10,MRC1, andTREM2, which were associated with an increased lipid deposition in multiple ectopic depots.

Conclusion:

Altered expression of macrophage-related genes in SAT is associated with differences in ectopic fat depot morphometrics among PWH on long-term ART, including in the pericardial and visceral compartments. These findings provide basis for future studies to assess host, virus, and treatment factors shaping the SAT immune environment and its effects on morphometric changes and metabolic comorbidities in PWH.
Ultrasound of the Normal and Abnormal Vas Deferens
Authors: Kerr Dana Middleton , Middleton William Dana
Published: February 2022

The extrapelvic portion of the vas deferens is readily visible with ultrasound but often overlooked. Several publications have described the scanning technique and the normal anatomy of the vas deferens. Sonographic evaluation of the vas deferens provides critical information in the workup of male infertility. Obstruction, inflammatory conditions, and neoplasms of the vas deferens can also be diagnosed with ultrasound. Knowledge of the normal and abnormal appearance of the vas deferens improves scans of the scrotum and expands the conditions that can be recognized and accurately diagnosed with ultrasound.
Perioperative Outcomes of Laparoscopic Liver Resection and Risk Factors for Adverse Events
Authors: Wiboonkhwan Nan-ak , Thongkan Tortrakoon , Sangkhathat Surasak , Pruphetkaew Nannapat , Pitakteerabundit Thakerng
Published: February 2022

Purpose:

The perioperative outcomes and risk factors associated with adverse events (AEs) after initial laparoscopic liver resection (LLR) are unclear. We studied the outcomes of LLR and identified the predictive factors for AEs.

Materials and Methods:

Data from 100 adults who underwent LLR between April 2014 and February 2020 were reviewed. Baseline characteristics, surgery details, intraoperative data, and postoperative outcomes were tabulated. The AEs included conversion to open surgery, morbidity, and mortality.

Results:

Major and minor LLRs accounted for 16% and 84% of cases, respectively. Of the indications for LLR, 88% were malignancies. Conversion to open surgery was necessary for 7% of the patients, the overall morbidity rate was 21%, the major morbidity rate was 7%, and the 90-day mortality rate was 1%. Although the incidence of AEs was higher after major LLR (37.5%) than after minor LLR (21.4%), the difference was not statistically significant (P=0.095); the rate of AEs in the resection of posterosuperior segments (43.7%) did not significantly differ from that of the anteroinferior segments (19.2%; P=0.095). Multivariable analysis revealed that the significant predictors of AEs included American Society of Anesthesiologists (ASA) class III (odds ratio, 5.76; 95% confidence interval, 1.74-19.1; P=0.003) and an operative time longer than 5 hours (odds ratio, 9.20; 95% confidence interval, 2.41-35.07; P<0.001).

Conclusion:

To improve outcomes in LLR, patients with ASA class III and those in whom surgery is expected to last longer than 5 hours should be taken into account for better patient selection.
Does a Cancer Diagnosis in Mid-to-Later Life Modify Racial Disparities in Memory Aging?
Authors: Eastman Marisa R. , Ospina-Romero Monica , Westrick Ashly C. , Kler Jasdeep S. , Glymour Medellena Maria , Abdiwahab Ekland , Kobayashi Lindsay C.
Published: February 2022

Background:

It is unknown whether an incident cancer diagnosis differentially impacts acute and long-term memory aging between older White and Black Americans.

Methods:

Incident cancer diagnoses and memory (immediate and delayed recall, combined with proxy-reported memory) were assessed at biennial study interviews in the US Health and Retirement Study (N=14,235, 1998-2016). We used multivariable segmented linear mixed-effects models to evaluate the rate of change in standardized memory score (SD/decade) in the years before, acutely at the time of, and in the years following an incident cancer diagnosis, compared to cancer-free adults, by race.

Results:

Black participants experienced faster memory decline than White participants (cancer-free group: −1.211 vs. −1.077; P<0.0001). An incident cancer diagnosis was associated with an acute memory drop in White, but not Black participants (−0.065 vs. 0.024; P<0.0001). However, White cancer survivors experienced slower memory decline than cancer-free White adults before and after diagnosis, but this memory advantage was not observed among Black cancer survivors.

Conclusions:

Racial disparities in memory aging are not modified by an incident cancer diagnosis. The acute cancer-related memory decline and long-term memory advantage experienced by White, but not Black, cancer survivors relative to cancer-free older adults, requires further investigation.
Psychotic disorders amid the COVID-19 pandemic: a consideration of risks and impacts
Authors: Tan Eric Josiah , Neill Erica , Rossell Susan Lee
Published: February 2022

Purpose of review

The COVID-19 pandemic has had a severe and widespread global impact but particularly for those with psychosis. This review summarizes recent evidence on the relationship between the COVID-19 pandemic and psychotic disorders, highlighting the risks faced by these individuals including the negative impacts on treatment services, complications from contracting COVID-19, and the acceptability of digital interventions.

Recent findings

Mortality, morbidity, and infection outcomes are among the worst for individuals with psychotic disorders. Presentation rates for psychotic disorders are elevated at emergency departments compared with before the COVID-19 pandemic; demand for inpatient services has increased, and there have been complications in access because of pandemic restrictions. COVID-19 related stressors have led to the exacerbation and incidence of psychotic symptoms among individuals with and without preexisting psychotic diagnoses. Digital interventions may be an acceptable method for maintaining patient contact and treatment during extended isolation.

More data is needed on the longitudinal trajectory for psychotic symptoms post-COVID-19 infection and pandemic restrictions to better support individuals with psychotic disorders. Development of a long-term pandemic management plan is needed to monitor and support psychiatric health across the population.
What happens after early intervention in first-episode psychosis? Limitations of existing service models and an agenda for the future
Authors: Hyatt Andrew S. , Hasler Victoria , Wilner Emily K.
Published: February 2022

Purpose of review

Early intervention in first-episode psychosis (FEP) improves symptomatic and functional outcomes while programs last. However, these gains may not be sustained over time and not all individuals benefit equally from such programs. This review examines the efficacy of FEP programs, as well as step-down practices and long-term outcomes to identify ways to extend the gains made in FEP programs.

Recent findings

FEP programs improve outcomes while services last, but effects diminish over time. Step-down and discharge practices vary widely with little randomized evidence guiding practice. Extending the duration of FEP programs for all does not consistently improve outcomes, but there is some encouraging evidence that targeted psychosocial interventions after program end may extend symptomatic and functional benefits. Members of marginalized groups and individuals with poorer outcomes during the FEP period may benefit from further specialized intervention after FEP.

Step down practices from FEP programs should be structured and tailored to individual needs, and benefit from sustained connections to community resources. Psychosocial interventions like social skills training, peer support, and supported education and employment may help extend the benefit of FEP programs after more intensive services end.
Palaeoecology of Cambrian–Ordovician acritarchs from China: evidence for a progressive invasion of the marine habitats
Authors: Shan Longlong , Yan Kui , Zhang Yuandong , Li Jun , Servais Thomas
Published: February 2022

Palaeozoic acritarchs mostly represent organic-walled cysts of marine phytoplankton, and therefore, as primary producers, played an important role in the evolution of marine ecosystems. In this study, we use a selection of the most abundant acritarch taxa from the Cambrian and Ordovician of China to understand the evolution of the palaeoecological patterns of the phytoplankton over the period. The taxa are attributed to 40 easily distinguishable morphotypes, of which the precise palaeoenvironmental distribution from 60 localities is available. By placing the 40 morphotypes on inshore–offshore transects it can be concluded that acritarch microfloras were limited to inshore environments during the early Cambrian, and progressively extended from inshore environments to offshore marine habitats during the later parts of the Cambrian and towards the Early Ordovician, with a prominent shift near the Cambrian–Ordovician boundary, confirming the onset of the ‘Ordovician plankton revolution’. In addition, the acritarch morphotypes evolved from low-diversity assemblages in the early Cambrian, dominated by simple spherical forms with limited ornamentation and simple process structures, to highly diverse assemblages with very complex morphologies in the Early and Middle Ordovician. During the Ordovician, the complex acritarch assemblages occupied most marine habitats, with palaeoecological distribution patterns similar to modern dinoflagellates.

This article is part of the theme issue ‘The impact of Chinese palaeontology on evolutionary research’.
Hominin evolution and diversity: a comparison of earlier-Middle and later-Middle Pleistocene hominin fossil variation in China
Authors: Liu Wu , Athreya Sheela , Xing Song , Wu Xiujie
Published: February 2022

Historical views of Asia as an evolutionary ‘backwater’ are associated with the idea that
Homo erectus
experienced long periods of stasis and ultimately went extinct. However, recent discoveries of well-dated Middle Pleistocene hominin fossils in China have considerably challenged these ideas and provide sufficient data to propose a testable model that explains the patterning of variation in Middle Pleistocene China, and why it changed over time. A series of hominin fossil studies comparing earlier-Middle and later-Middle Pleistocene groups confirm that the expressions of certain traits shift around 300 ka. Fossils from the later Middle Pleistocene are more variable with a mix of archaic traits as well as ones that are common in Western Eurasian early
Homo sapiens
and Neanderthals. The period around 300 ka appears to have been a critical turning point for later-Middle Pleistocene morphological changes in China. It coincides with a phase of climatic instability in the Northern Hemisphere between Marine Isotope Stages 12 and 10 that would have led to changes in gene flow patterning, and regional population survival/extinction. This localized and testable model can be used for future explorations of hominin evolution in later Pleistocene eastern Eurasia.

This article is part of the theme issue ‘The impact of Chinese palaeontology on evolutionary research’.
Flavobacterium endoglycinae sp. nov., an endophytic bacterium isolated from soybean (Glycine max L. cv. Gwangan) stems
Authors: Seo Jiyoon , Peng Yuxin , Jiang Lingmin , Lee Sang-Beom , Jeong Rae-Dong , Park Soon Ju , Kim Cha Young , Choi Man-Soo , Lee Jiyoung
Published: February 2022

A Gram-stain-negative, facultatively anaerobic, motile by gliding, rod-shaped, oxidase- and catalase-positive bacterial strain, designated BB8T, was isolated from the stems of a Korean soybean cultivar (Glycine max L. cv. Gwangan). The strain produced a yellow pigment on tryptic soy agar. Growth of strain BB8T occurred at pH 5.0–8.0 (optimum, pH 7.0), at 10–35 °C (optimum, 25–30 °C) and in the presence of 0–1 % (w/v) NaCl (optimum, 0.5%). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain BB8T formed a lineage within the genus

Flavobacterium

and was most closely related to

Flavobacterium artemisiae

SYP-B1015T (96.9 % 16S rRNA gene sequence similarity) and

Flavobacterium ustbae

T13T (96.8%). The complete genome sequence of strain BB8T was 5 513 159 bp long with a G+C content of 34.1 mol%. The major fatty acids (>10 %) of strain BB8T were iso-C15 : 0 (21 %), summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c, 20.3%) and iso-C16 : 0 3-OH (13.7%). The predominant polar lipids were phosphatidylethanolamine and unidentified aminolipids, and the major respiratory quinone was menaquinone-6. Based on these phenotypic, genotypic and chemotaxonomic characteristics, strain BB8T is considered to represent a novel species of the genus

Flavobacterium

, for which the name Flavobacterium endoglycinae sp. nov. is proposed. The type strain is BB8T (=KCTC 82167T=CCTCC AB 2020070T).
Presence of optrA-mediated linezolid resistance in multiple lineages and plasmids of Enterococcus faecalis revealed by long read sequencing
Authors: McHugh Martin P. , Parcell Benjamin J. , Pettigrew Kerry A. , Toner Geoff , Khatamzas Elham , el Sakka Noha , Karcher Anne Marie , Walker Joanna , Weir Robert , Meunier Danièle , Hopkins Katie L. , Woodford Neil , Templeton Kate E. , Gillespie Stephen H. , Holden Matthew T. G.
Published: February 2022

Transferable linezolid resistance due to optrA, poxtA, cfr and cfr-like genes is increasingly detected in enterococci associated with animals and humans globally. We aimed to characterize the genetic environment of optrA in linezolid-resistant

Enterococcus faecalis

isolates from Scotland. Six linezolid-resistant

E. faecalis

isolated from urogenital samples were confirmed to carry the optrA gene by PCR. Short read (Illumina) sequencing showed the isolates were genetically distinct (>13900 core SNPs) and belonged to different MLST sequence types. Plasmid contents were examined using hybrid assembly of short and long read (Oxford Nanopore MinION) sequencing technologies. The optrA gene was located on distinct plasmids in each isolate, suggesting that transfer of a single plasmid did not contribute to optrA dissemination in this collection. pTM6294-2, BX5936-1 and pWE0438-1 were similar to optrA-positive plasmids from China and Japan, while the remaining three plasmids had limited similarity to other published examples. We identified the novel Tn6993 transposon in pWE0254-1 carrying linezolid (optrA), macrolide (ermB) and spectinomycin [ANT(9)-Ia] resistance genes. OptrA amino acid sequences differed by 0–20 residues. We report multiple variants of optrA on distinct plasmids in diverse strains of

E. faecalis

. It is important to identify the selection pressures driving the emergence and maintenance of resistance against linezolid to retain the clinical utility of this antibiotic.
Best Practices on Big Data Analytics to Address Sex-Specific Biases in our Understanding of the Etiology, Diagnosis and Prognosis of Diseases
Authors: Golder Su , O’Connor Karen , Wang Yunwen , Stevens Robin , Gonzalez-Hernandez Graciela
Published: February 2022

A bias in health research to favor understanding of diseases as they present in men can have a grave impact on the health of women. This paper reports on a conceptual review of the literature that used machine learning or NLP techniques to interrogate big data for identifying sex-specific health disparities. We searched Ovid MEDLINE, Embase, and PsycINFO in October 2021 using synonyms and indexing terms for (1) “women” or “men” or “sex,” (2) “big data” or “artificial intelligence” or “NLP”, and (3) “disparities” or “differences.” From 902 records, 22 studies met the inclusion criteria and were analyzed. Results demonstrate that the inclusion by sex is inconsistent and often unreported, although the inclusion of men in the included studies is disproportionately less than women. Even though AI and NLP techniques are widely applied in health research, few studies use them to take advantage of unstructured text to investigate sex-related differences or disparities. Researchers are increasingly aware of sex-based data bias, but the process towards correction is slow. We reflected on what would be the best practices on using big data analytics to address sex-specific biases in understanding the etiology, diagnosis, and prognosis of diseases.
Preferential activation of proprioceptive and cutaneous sensory fibers compared to motor fibers during cervical transcutaneous spinal cord stimulation: A computational study
Authors: de Freitas Roberto M. , Capogrosso Marco , Nomura Taishin , Milosevic Matija
Published: February 2022

Objective

Cervical transcutaneous spinal cord stimulation (tSCS) is a promising technology that can support motor function recovery of upper-limbs after spinal cord injury. Its efficacy may depend on the ability to recruit sensory afferents and convey excitatory inputs onto motoneurons. Therefore, understanding its physiological mechanisms is critical to accelerate its development towards clinical applications. In this study, we used an anatomically realistic computational model of the cervical spine to compare α-motor, Aα-sensory, and Aβ-sensory fiber activation thresholds and activation sites.

Approach

We developed a tridimensional geometry of the cervical body and tSCS electrodes with a cathode centred at the C7 spinous process and an anode placed over the anterior neck. The geometrical model was used to estimate the electric potential distributions along motor and sensory fiber trajectories at the C7 spinal level using a finite element method. We implemented dedicated motor and sensory fiber models to simulate the α-motor and Aα-sensory fibers using 12, 16, and 20 μm diameter fibers, and Aβ-sensory fibers using 6, 9, and 12 μm diameter fibers. We estimated nerve fiber activation thresholds and sites for a 2 ms monophasic stimulating pulse and compared them across the fiber groups.

Main results

Our results showed lower activation thresholds of Aα- and Aβ-sensory fibers compared with α-motor fibers, suggesting preferential sensory fiber activation. We also found no differences between activation thresholds of Aα-sensory and large Aβ-sensory fibers, implying they were co-activated. The activation sites were located at the dorsal and ventral root levels.

Significance

Using a realistic computational model, we demonstrated preferential activation of dorsal root Aα- and Aβ-sensory fibers compared with ventral root α-motor fibers during cervical tSCS. These findings suggest high proprioceptive and cutaneous contributions to neural activations during cervical tSCS, which inform the underlying mechanisms of upper-limb functional motor recovery.
Abnormal molecular signatures of inflammation, energy metabolism and vesicle biology in human Huntington disease peripheral tissues
Authors: Neueder Andreas , Kojer Kerstin , Hering Tanja , Lavery Daniel J. , Chen Jian , Birth Nathalie , Hallitsch Jaqueline , Trautmann Sonja , Parker Jennifer , Flower Michael , Sethi Huma , Haider Salman , Lee Jong-Min , Tabrizi Sarah J. , Orth Michael
Published: February 2022

Background

A major challenge in neurodegenerative diseases concerns identifying biological disease signatures that track with disease progression or respond to an intervention. Several clinical trials in Huntington disease (HD), an inherited, progressive neurodegenerative disease, are currently ongoing. Therefore, we examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in HD patients.

Results

We generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue to probe molecular changes in human premanifest and early manifest HD patients – those most likely involved in clinical trials. In-depth single nucleotide polymorphism data across the HTT gene will facilitate the use of the generated primary- and iPSC cell lines in allele-specific targeting approaches. The analysis of the transcriptomics and proteomics data shows robust, stage-dependent dysregulation. Gene ontology analysis confirmed the involvement of inflammation and energy metabolism in peripheral HD pathogenesis. Furthermore, we observed changes in the homeostasis of extracellular vesicles, where we found consistent changes of genes and proteins involved in this process.

Conclusions

Our ‘omics data document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials. Together with the primary cell lines established from peripheral tissues and a large panel of iPSC lines that can serve as human models of HD, the generated data are a valuable and unique resource to advance the current understanding of molecular mechanisms driving HD pathogenesis.
Uncovering the hologenomic basis of an extraordinary plant invasion
Authors: Bieker Vanessa C. , Battlay Paul , Petersen Bent , Sun Xin , Wilson Jonathan , Brealey Jaelle C. , Bretagnolle François , Nurkowski Kristin , Lee Chris , Owens Gregory L. , Lee Jacqueline Y. , Kellner Fabian L. , van Boheeman Lotte , Gopalakrishnan Shyam , Gaudeul Myriam , Mueller-Schaerer Heinz , Karrer Gerhard , Chauvel Bruno , Sun Yan , Dalén Love , Poczai Péter , Rieseberg Loren H. , Gilbert M. Thomas P. , Hodgins Kathryn A. , Martin Michael D.
Published: February 2022

While invasive species are a key driver of the global biodiversity crisis, the drivers of invasiveness remain debated. To investigate the genomic basis of invasiveness in plants, we use the invasive weed Ambrosia artemisiifolia, introduced to Europe in the late 19th century, resequencing 655 ragweed genomes, including 308 herbarium specimens collected up to 190 years ago. In introduced European populations, we report selection signatures in defense genes and lower prevalence of particular plant pathogens in the invasive range. Together with temporal changes in population structure associated with introgression from closely related Ambrosia species, escape from microbial enemies likely favoured the plant’s remarkable success as an invasive species.

One-Sentence Summary

The invasive success of European ragweed was facilitated by release from enemy microbes and inter-species hybridization.
CRFalign: A Sequence-structure alignment of proteins based on a combination of HMM-HMM comparison and conditional random fields
Authors: Lee Sung Jong , Joo Keehyoung , Sim Sangjin , Lee Juyong , Lee In-Ho , Lee Jooyoung
Published: February 2022

We built a method of sequence-structure alignment (called CRFalign) which improves upon a base alignment model based on HMM-HMM comparison by employing pairwise conditional random fields (pCRF) in combination with nonlinear scoring functions of structural and sequence features. The total scoring function consists of a base scoring part based on HMM-HMM profile comparison plus additional nonlinear scoring part which is implemented by a set of gradient boosted regression trees. In addition to sequence profile features, various structural features are employed including secondary structures, solvent accessibilities, environment-dependent properties that give rise to position-dependent as well as environment-dependent match scores and gap penalties. Training is performed on reference alignments at superfamily levels or twilight zone chosen from the SABmark benchmark set. We found that our alignment method produce relative improvement in terms of average alignment accuracies, especially for the alignment of remote homologous proteins. We found that our alignment method produced (by using Modeller) better modeling results especially in the relatively hard targets compared with other methods. CRFalign was successfully applied to the stages of fold recognition and multiple sequence alignment in CASP11 and CASP12 competition on protein structure predictions.