bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimedia Learning
Authors: Mayer Richard E.
Published: February 2022

This article defines and exemplifies multimedia learning and multimedia instruction, describes theoretical frameworks for multimedia learning and multimedia instruction, summarizes evidence-based principles for how to design multimedia instruction, and suggests future trends in multimedia research. Multimedia design principles for reducing extraneous processing include the coherence principle, signaling principle, redundancy principle, spatial contiguity principle, and temporal contiguity principle. Multimedia design principles for managing essential processing include the pre-training principle, segmenting principle, and modality principle. Multimedia design principles for fostering generative processing include the personalization principle, voice principle, embodiment principle, and generative activity principle. Research on multimedia learning represents an example of applying the science of learning to education, and stands as one of educational psychology’s success stories.
An evolutionarily conserved C4HC3-type E3 ligase regulates plant broad-spectrum resistance against pathogens
Authors: Fu Shuai , Wang Kun , Ma Tingting , Liang Yan , Ma Zhonghua , Wu Jianxiang , Xu Yi , Zhou Xueping
Published: February 2022

Deployment of broad-spectrum disease resistance against multiple pathogen species is an efficient way to control plant diseases. Here, we identify a Microtubule-associated C4HC3-type E3 Ligase (MEL) in both Nicotiana benthamiana and Oryza sativa, and show that it is able to integrate and initiate a series of host immune signaling, conferring broad-spectrum resistance to viral, fungal, and bacterial pathogens. We demonstrate that MEL forms homodimer through intermolecular disulfide bonds between its cysteine residues in the SWIM domain, and interacts with its substrate serine hydroxymethyltrasferase 1 (SHMT1) through the YφNL motif. Ubiquitin ligase activity, homodimerization and YφNL motif are indispensable for MEL to regulate plant immunity by mediating SHMT1 degradation through the 26S proteasome pathway. Our findings provide a fundamental basis for utilizing the MEL–SHMT1 module to generate broad-spectrum-resistant rice to global destructive pathogens including rice stripe virus, Magnaporthe oryzae, and Xanthomonas oryzae pv. oryzae.
Nailfold capillaroscopy in SSc: innocent bystander or promising biomarker for novel severe organ involvement/progression?
Authors: Vanhaecke Amber , Cutolo Maurizio , Distler Oliver , Riccieri Valeria , Allanore Yannick  , Denton Christopher P , Hachulla Eric , Ingegnoli Francesca , Deschepper Ellen  , Avouac Jérôme , Jordan Suzana , Launay David , Melsens Karin , Pizzorni Carmen , Sulli Alberto , Vasile Massimiliano , Herrick Ariane L , Smith Vanessa 
Published: February 2022

Objectives

Nailfold videocapillaroscopy (NVC) plays a well-established role in differentiating primary from secondary RP due to SSc. However, the association of NVC with novel severe organ involvement/progression in SSc has never been evaluated in a multicentre, multinational study, which we now perform for the first time.

Methods

Follow-up data from 334 SSc patients [265 women; 18 limited SSc (lSSc)/203 lcSSc/113 dcSSc] registered between November 2008 and January 2016 by seven tertiary centres in the EUSTAR-database, were analysed. Novel severe organ involvement/progression was defined as new/progressive involvement of the peripheral vasculature, lungs, heart, skin, gastrointestinal tract, kidneys, musculoskeletal system, or death, at the 12- or 24-month follow-up. NVC images at enrolment were quantitatively and qualitatively evaluated according to the standardized definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases. Uni- and multivariable logistic regression modelling (ULR, MLR) was performed.

Results

Of the 334 included SSc patients, 257 (76.9%) developed novel overall severe organ involvement/progression. Following MLR, normal capillary density was associated with less-frequent novel overall severe organ involvement/progression [odds ratio (OR) = 0.77, P < 0.001] and novel peripheral vascular involvement (OR = 0.79, P = 0.043); microhaemorrhages were associated with less novel pulmonary hypertension (OR = 0.47, P = 0.029); and a ‘severe’ (active/late) NVC pattern was associated with novel overall severe organ involvement/progression (OR = 2.14, P = 0.002) and skin progression (OR = 1.70, P = 0.049).

Conclusions

Our results suggest that NVC may be a promising biomarker in SSc, certainly warranting further investigation. Despite the participation of tertiary centres, which follow their patients in a standardized way, we were underpowered to detect associations with infrequent severe organ involvement/progression.
Comparison of Acute Followed by Maintenance ECT vs Clozapine on Psychopathology and Regional Cerebral Blood Flow in Treatment-Resistant Schizophrenia: A Randomized Controlled Trial
Authors: Mishra Biswa Ranjan , Agrawal Kanhaiyalal , Biswas Tathagata , Mohapatra Debadatta , Nath Santanu , Maiti Rituparna
Published: February 2022

Background and Hypothesis

In treatment-resistant schizophrenia (TRS), Clozapine is only approved treatment with undesirable side-effects, warranting better alternatives. Our hypothesis is acute followed by maintenance Electroconvulsive Therapy (M-ECT) will be comparable in efficacy and safety to Clozapine in TRS.

Study Design

In this open-label trial, 60 TRS patients were randomized equally to M-ECT (following an acute-course) or Clozapine. Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Schizophrenia Scale (CGI-SCH), Montreal Cognitive Assessment (MoCA), and Global assessment of functioning (GAF) were measured and compared within and between the groups at baseline, 6 weeks, 12 weeks, and 24 weeks. SPECT-CT brain was done at baseline and 24 weeks to compare the changes in regional cerebral perfusion between the groups and correlate with the changes in the outcome-measures.

Study Results

The PANSS-T scores changes from baseline over the observation-points were significant in both M-ECT and clozapine groups (P < .001), with comparatively better reduction with M-ECT (P < .001). Similar trends were observed in PANSS subscales, CGI-SCH and GAF in both groups, with significantly better improvement with M-ECT over the study-period. After 24 weeks, there was significantly better perfusion with M-ECT in bilateral prefrontal and temporal cortices (P < .05). With M-ECT, a positive correlation was found between changes in PANSS-P scores and left-lateral Temporal cortical perfusion (r = .465, P = .017).

Conclusions

Acute followed by M-ECT was more effective than clozapine over 6 months in reducing the positive and negative symptoms, general psychopathology, illness-severity, and improving the global functionality in TRS [clinicaltrials.gov: NCT03807882].
Lucid dreaming occurs in activated rapid eye movement sleep, not a mixture of sleep and wakefulness
Authors: Baird Benjamin , Tononi Giulio , LaBerge Stephen
Published: February 2022

Study Objectives

(1) To critically test whether a previously reported increase in frontolateral 40 Hz power in lucid REM sleep, used to justify the claim that lucid dreaming is a “hybrid state” mixing sleep and wakefulness, is attributable to the saccadic spike potential (SP) artifact as a corollary of heightened REM density. (2) To replicate the finding that lucid dreams are associated with physiological activation, including heightened eye movement density, during REM sleep. (3) To conduct an exploratory analysis of changes in EEG features during lucid REM sleep

Methods

We analyzed 14 signal-verified lucid dreams (SVLDs) and baseline REM sleep segments from the same REM periods from six participants derived from the Stanford SVLD database. Participants marked lucidity onset with standard left-right-left-right-center (LR2c) eye-movement signals in polysomnography recordings.

Results

Compared to baseline REM sleep, lucid REM sleep had higher REM density (β = 0.85, p = 0.002). Bayesian analysis supported the null hypothesis of no differences in frontolateral 40 Hz power after removal of the SP artifact (BH = 0.18) and ICA correction (BH = 0.01). Compared to the entire REM sleep period, lucid REM sleep showed small reductions in low-frequency and beta band spectral power as well as increased signal complexity (all p < 0.05), which were within the normal variance of baseline REM sleep.

Conclusions

Lucid dreams are associated with higher-than-average levels of physiological activation during REM sleep, including measures of both subcortical and cortical activation. Increases in 40 Hz power in periorbital channels reflect saccadic and microsaccadic SPs as a result of higher REM density accompanying heightened activation.
Swallowing and aspiration during sleep in patients with obstructive sleep apnea versus control individuals
Authors: Kohno Akane , Kohno Masaki , Ohkoshi Shogo
Published: February 2022

Study Objectives

There are only a few reports on voluntary swallowing during sleep; therefore, this study aimed to propose a method for observing voluntary swallowing during sleep using polysomnography. The frequency of voluntary swallowing during sleep and the factors related to swallowing and aspiration during sleep were investigated.

Methods

Polysomnography records of 20 control subjects and 60 patients with obstructive sleep apnea (OSA) (mild, moderate, and severe groups; n = 20 each) were collected. Simultaneous increases in the electromyographic potentials of the submental and masseter muscles, termed coactivation, and declining oronasal airflow (SA) were extracted as “swallowing.” The cough reflex that occurred during sleep was extracted as “aspiration.” The frequency of swallowing events was compared among the different OSA severity groups. Subsequently, a multivariate regression analysis was performed.

Results

The average frequency of coactivation with SA in control subjects was 4.1 events/h and that without SA was 1.7 events/h. These frequencies increased with the severity of OSA during non-REM sleep. The distance of the hyoid to the Frankfurt plane was associated with the frequency of coactivation with (β = 0.298, p = 0.017) as well as without SA (β = 0.271, p = 0.038). The frequency of coactivation without SA was associated with aspiration (B = 0.192, p = 0.042).

Conclusions

Our data provide new insights into the relationship between swallowing and aspiration during sleep. We found that the longer the distance from the hyoid bone to the Frankfurt plane, the higher the coactivation without SA, which could lead to aspiration during sleep.

Clinical Trials

Retrospective observational study of swallowing during sleep in obstructive sleep apnea patients using polysomnography, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000050460, UMIN000044187.
Effect of Antenatal Dexamethasone in Late Preterm Period on Neonatal Hypoglycemia: A Prospective Cohort Study from a Developing Country
Authors: Pal Somnath , Sardar Syamal , Sarkar Nirmalya , Ghosh Moumita , Chatterjee Suparna
Published: February 2022

Objectives

This study compared the risk of hypoglycemia within 72 h of life in infants with and without exposure to antenatal dexamethasone in the late preterm period (34–366/7 week’s gestational age).

Methods

This prospective cohort study was conducted in a tertiary care neonatal unit of Eastern India from May 2021 to November 2021. Babies in the exposed group received at least one dose of antenatal dexamethasone in the late preterm period between 7 days before delivery and birth. ‘Complete course’ of antenatal steroid was defined as four doses of injection dexamethasone at 12 h intervals and <4 doses were considered as ‘Partial course’. Primary outcome was incidence of hypoglycemia within 72 h of life, defined as whole blood glucose <45 mg/dl.

Results

Total 298 infants (98 in control, 134 in partial and 66 in complete group) were assessed for final outcome. No significant difference in outcomes were seen in the exposed group compared to unexposed group. However, incidence of hypoglycemia within 72 h (complete vs. partial p= 0.008, complete vs. control p=0.005) and 12 h of life (complete vs. partial p=0.013, complete vs. control p=0.013) was significantly less in complete steroid group. Logistic regression analysis revealed complete course of antenatal corticosteroid significantly decreased the risk of hypoglycemia [adjusted odds ratio, 95% confidence interval (CI) 0.15 (0.03–0.69), p=0.015]. Number needed to be exposed for one additional benefit was 7 (95% CI, 6.35–22.14).

Conclusion

Complete course of dexamethasone administered to mothers at risk of late preterm delivery reduces risk of neonatal hypoglycemia within 72 h of life.
Initiating Long-acting Injectable Naltrexone: Procedure for a Second Attempt After a First Attempt Fails
Authors: Shulman Matisyahu , Hu Mei Chen , Nunes Edward V. , Bisaga Adam
Published: February 2022

Background and Objective

Many patients are unable to initiate long-acting injectable naltrexone (XR-NTX) on a first attempt, due to the prerequisite abstinence and withdrawal from opioids.

Methods

Thirty patients who were unable to initiate XR-NTX were recruited to receive buprenorphine for 1 week, followed by a 3-week buprenorphine taper, and an ascending titration of oral naltrexone before XR-NTX injection.

Results

Eight (27%) initiated XR-NTX, 7 (23%) transitioned to buprenorphine maintenance treatment and 15 (50%) were lost to follow up.

Conclusion and Scientific Significance

A second attempt at XR- NTX initiation using buprenorphine stabilization and cross taper may be a reasonable approach for some patients.
Review of Lasers and Energy-Based Devices for Skin Rejuvenation and Scar Treatment With Histologic Correlations
Authors: Chen Stella X. , Cheng Judy , Watchmaker Jacqueline , Dover Jeffrey S. , Chung Hye Jin
Published: February 2022

BACKGROUND

Lasers and energy-based devices (EBD) are popular treatments for skin rejuvenation and resurfacing. Achieving desired outcomes and avoiding complications require understanding the effects of these devices at a histologic level. Currently, no comprehensive review summarizing the histologic effects of laser and energy-based treatments exists.

OBJECTIVE

To describe how lasers and EBD alter skin histology and improve the overall understanding of these devices.

MATERIALS AND METHODS

A PubMed search was conducted for studies with histologic analysis of fractional picosecond laser, fractional radiofrequency microneedling, nonablative lasers, and ablative lasers.

RESULTS

Fractional picosecond lasers induce intraepidermal and/or dermal vacuoles from laser-induced optical breakdown. Fractional radiofrequency microneedling delivers thermal energy to the dermis while sparing the epidermis, making it safer for patients with darker skin phototypes. Fractional nonablative lasers induce conical zones of coagulation of the epidermis and upper dermis. Ablative lasers vaporize the stratum corneum down to the dermis. Traditional ablative lasers cause diffuse vaporization while fractional ablative lasers generate columns of tissue ablation.

CONCLUSION

Lasers and EBD are effective for skin resurfacing and rejuvenation and have different mechanisms with disparate targets in the skin. Safe and effective use of devices requires understanding the histologic laser–tissue interaction.
Pyoderma Gangrenosum after Breast Cancer Resection: A Less-invasive and Early Treatment Using the Skin around Ulcers
Authors: Hirai Kotaro , Tsuge Itaru , Usui Shunya , Takada Masahiro , Yamanaka Hiroki , Katsube Motoki , Sakamoto Michiharu , Morimoto Naoki
Published: February 2022

Surgical invasion is a risk factor of pyoderma gangrenosum (PG). A total of 25% of postoperative PG cases were reported to occur after breast surgeries, including bilateral breast reduction and breast reconstruction following cancer resection. Immunosuppressive therapy and less-invasive wound therapy are necessary; however, the complete healing of ulcers takes 5.1 months on average. We herein report a case of skin grafting under a surgical concept of less-invasive and short-term treatment. An 82-year-old woman complained of a high fever and severe pain at her breast wounds after bilateral breast cancer resection. Although we performed emergency debridement surgery to remove the necrotic tissue, suspecting surgical site infection and inflammation, her high fever persisted. She was diagnosed with PG because of the physical findings of characteristic painful, sterile ulcerations, bullae and pustules, and the pathological abundance of neutrophils in the absence of infection and vasculitis. Oral administration of prednisolone 30 mg/day improved the symptoms, and we applied negative-pressure wound therapy (NPWT) from day 16 following debridement surgery. After the gradual reduction of oral steroid intake to 12.5 mg/day, we performed skin grafting surgery. To limit the surgical invasion, we used the surplus skin around the ulcers. Split-thickness mesh skin grafts were fixed by NPWT to avoid the use of tie-over sutures. We achieved short-term treatment of PG with a less-invasive surgical strategy using skin around the ulcers and NPWT.
Cleft Lip and Palate Research in Low- and Middle-income Countries: A Scientometric Analysis
Authors: Kanmounye Ulrick Sidney , Dutton John L. , Naidu Priyanka , Msokera Chifundo , Collier Zachary J. , Fernanda Tapia Maria , Mikhail Shady , Xepoleas Meredith , Auslander Allyn , Yao Caroline A. , Magee William
Published: February 2022

Background:

Cleft lip and palate (CLP) comprise over 90% of the world’s congenital anomalies and cause significant disability worldwide, while disproportionally burdening low- and middle-income countries (LMICs). Research can help inform strategies that reduce disparities in accessing CLP care. We performed a scientometric analysis of CLP research in LMICs to identify influential contributors and themes.

Methods:

The authors searched seven citation databases accessed via Web of Science, from inception to March 2, 2021. Social network analysis was done using VOSviewer. The Kruskal-Wallis test and linear regression were used.

Results:

In total, 1561 articles authored by 6414 researchers affiliated with 2113 organizations in 119 countries were included. Most authors (n = 6387, 99.6%) had published two or more articles. The USA (454 articles), Brazil (211 articles), China (175 articles), and India (127 articles) published the most. The most prolific institutions were the University of Sao Paulo (94 articles), the University of Pittsburgh (57 articles), and the University of Iowa (55 articles). Marazita ML (33 articles), Shi B (27 articles), and Murray JC (22 articles) had the highest number of publications. An estimated 510 articles (32.7%) were focused on epidemiology, 240 (15.4%) on management, and 54 (3.5%) on global plastic surgery for CLP.

Conclusions:

LMICs are disproportionally burdened by CLP, but research is limited and often produced by high-income countries. This study elucidates partnership and health system strengthening opportunities to improve LMIC research capacity and ultimately informs the management and outcomes for patients with CLP.
Advancing bacteriophages as a treatment of antibiotic-resistant bacterial pulmonary infections
Authors: Satta Giovanni , O’Callagharn Christopher , Clokie Martha R.J. , Di Luca Mariagrazia
Published: February 2022

Purpose of review

The current article summarizes the recent advances in the use of bacteriophages to treat pulmonary infections, particularly those caused by Gram-negative drug-resistant bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Burkholderia species. It provides an updated overview of the current available evidence, with a summary of published clinical cases, case series and clinical trials currently underway.

Recent finding Personalized treatment with bacteriophages is still in its infancy in Europe and the USA, despite extensive experience in Eastern countries. However, more patients are expected to be treated with clinical trials in progress and others planned.

Despite very promising initial results and the confirmation of phage safety, there are still many ethical and practical implications to be considered, from the necessary regulatory approval to optimization of dose and route of administration, to developing strategies to tackle bacterial resistance. Patients with cystic fibrosis are a group where phage therapy, if successful, could have a major impact.
Finerenone: a new mineralocorticoid receptor antagonist to beat chronic kidney disease
Authors: Raj Rajesh
Published: February 2022

Purpose of review

Clinical trials of the mineralocorticoid receptor antagonist (MRA) finerenone published recently suggest that they improve outcomes in patients with diabetic kidney disease (DKD). This review summarises key research from the last two years to provide clinicians with a synopsis of recent findings.

Recent findings

Large international trials, such as Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (5674 participants) and Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (7437 participants), suggest that in proteinuric patients with DKD and estimated glomerular filtration rate >25 ml/min/1.73 m2, already on renin-angiotensin-aldosterone system inhibitors, addition of finerenone provided modest further improvement in composite renal and cardiovascular outcomes. Proteinuria was reduced; there was also a small drop in systolic blood pressure. Hyperkalaemia remained a concern, although the incidence is lower with finerenone. Emerging data suggest that newer potassium binding agents may mitigate this risk. Preclinical studies suggest additive benefits when MRA and sodium-glucose co-transporter 2 (SGLT-2) inhibitors are used in combination.

The nonsteroidal MRA finerenone could improve renal and cardiac outcomes further in diabetics with kidney disease when added to renin-angiotensin system inhibitors. Hyperkalaemia is probably less worrisome, but real-world data is needed. Combinations with other new nephroprotective agents (such as SGLT2i inhibitors) has the potential to provide increasing benefit. Benefits of finerenone in chronic kidney disease without diabetes remains to be seen.
Correlation of preoperative PET/computer tomography 18F-fluorodeoxyglucose uptake (maximum standardized uptake value) with prognosis in patients with operated lung cancer
Authors: Mertoğlu Aydan , Üçvet Ahmet , Balci Günseli , Aksel Nimet , Batum Özgür , Cireli Emel , Ceylan Kenan Can , Koparal Hakan , Çirak Ali Kadri , Gürsoy Soner , Yilmaz Ufuk , Kömürcüoğlu Berna
Published: February 2022

Purpose

The aim of this study was to investigate the correlation of preoperative 18F-fluorodeoxyglucose PET/computed tomography maximum standardized uptake value (SUVmax) in operated non-small cell lung cancer (NSCLC) cases with other prognostic parameters and survival.

Patients and methods

NSCLC patients treated by surgical resection were imaged with PET within 60 days before surgery.

Results

Overall, 525 cases consecutive patients were retrospectively reviewed. The median value of SUVmax in a total of 525 cases was 12.1, and the mean was 13.3 ± 7.13. Logistic regression analysis performed to identify the variables that have an impact on SUVmax revealed that histology [hazard ratio (HR: 1.893; 95% CI; P = 0.001) and T status (HR: 8.991; 95% CI; P = 0.000) are correlated with SUVmax. Kaplan–Meier analysis revealed a mean survival of 73.7 ± 1.95 months and a median survival of 85.6 ± 6.03 months. In the group with an SUVmax value of less than 10, the mean survival was 81.9 ± 3.02 months (76.0–87.8), and in the group with SUVmax greater than 10.1, the mean survival was 68.6 ± 2.4 months (63.9–73.3) (P = 0.000). In the multivariate analysis, SUVmax, age, tumor histology, lymph node metastasis, comorbid diseases and complete/incomplete status of the resection were identified as the factors predictive of prognosis.

Conclusion

It is seen that preoperative SUVmax is a parameter with prognostic significance at least as much as histopathology, age, complete/incomplete status of resection and lymph node involvement.
The expanding role of lyso-phosphatidylcholine acyltransferase-3 (LPCAT3), a phospholipid remodeling enzyme, in health and disease
Authors: Lagrost Laurent , Masson David
Published: February 2022

Purpose of review

The turnover of fatty acids (FAs) at the sn-2 position of phospholipids is mediated by the reciprocal actions of phospholipases A2 and lyso-PL acyltransferases (LPLAT). LPCAT3, a major LPLAT isoform, exhibits a strong specificity for polyunsaturated FAs s (PUFAs). Although the enzyme was originally studied in the context of cardiometabolism, recent investigations have shed light on the role of LPCAT3 in other tissues such as skeletal muscle and in unexpected biological processes such as cell death and oncogenesis.

Recent findings

The three-dimensional structure of LPCAT3 has been elucidated allowing further understanding of the mechanism of the acylation reaction as well as the substrate specificity of the enzyme. In skeletal muscle, LPCAT3-mediated phospholipid remodeling modulates membrane domain clustering and insulin signaling

LPCAT3 plays an important role in the process of ferroptosis by modulating the PUFA content of phospholipids and possibly of plasmalogens.

In tumor-associated macrophages, LPCAT3 can prevent ER stress induced by the tumor microenvironment and may equally modulate antitumor immunity.

LPCAT3 is an attractive therapeutic target in the cardiometabolic disorders. Nevertheless, the involvement of LPCAT3 in processes such as cell death and oncogenesis demands caution with respect to the potential deleterious effects of enzyme modulation.
Closing the abdomen: update on the current surgical toolkit
Authors: Amin Irum , Canovai Emilio
Published: February 2022

Purpose of review

Achieving abdominal wall closure after intestinal transplantation (ITx) is one of the crucial surgical challenges. This problem is present in 25–50% of all transplants due to reduction in abdominal domain, fistulae and extensive adhesions due to previous surgeries. Failure to achieve closure is an independent risk factor for mortality and graft loss. The aim of this paper is to summarize the current options to achieve this.

Recent findings

Successful closure of the abdomen requires a tension-free repair. Primary closure of the fascia can be reinforced with synthetic or biological mesh. For more complex fascial defects bridging mesh, nonvascularised or vascularised rectus fascia can be utilised. If all components of the abdominal wall are affected, then a full-thickness abdominal wall transplantation may be necessary.

A variety of successful techniques have been described by different groups to enable abdominal wall closure after ITx. Emerging developments in preoperative imaging, reconstructive surgery and immunology have expanded the surgical toolkit available. Crucial is a tailor-made approach whereby patients with expected closure issues are identified prior to surgery and the simplest technique is chosen.
Are We Working Harder for Less Pay? A Survey of Medicare Reimbursement for Hand and Upper Extremity Surgery
Authors: Nayar Suresh K. , Wollstein Adi , Sullivan Brian T. , Kreulen R. Timothy , Sabharwal Samir , Tuffaha Sami H. , LaPorte Dawn M. , Chen Neal C. , Eberlin Kyle R.
Published: February 2022

Background:

Ongoing concern for declining Medicare payment to surgeons may incentivize surgeons to perform more cases to maintain productivity goals. The authors evaluated trends in physician payment, patient charges, and reimbursement ratios for the most common hand and upper extremity surgical procedures.

Methods:

The authors examined Medicare surgeon payment, patient charges, and surgical volume from 2012 to 2017 for 83 common surgical procedures, incorporating the year-to-year Consumer Price Index to adjust for inflation. The reimbursement ratio was calculated by dividing payment by charge. Weighted (by surgery type and volume) averages were calculated.

Results:

Total Medicare surgeon payment increased 5.6 percent to $272 million for the studied procedures. Patient charges were seven times greater than payment, growing 24 percent to $1.9 billion. Despite growth of total payment, the average overall weighted payment for a single surgery decreased 3.5 percent. The average weighted patient charge increased 8 percent, whereas the reimbursement ratio decreased 13 percent. A hand surgeon would need to perform three more cases per 100 in 2017 to maintain the same reimbursement received in 2012. After categorizing these 83 surgical procedures, distal radius fixation (>3 parts, 21 percent increase; >2-part intra-articular, extra-articular, and percutaneous pinning, 17 percent increase), bony trauma proximal to the distal radius (10 percent increase), and upper extremity flap (5 percent increase) were subject to the greatest increases in payment. Payment for forearm fasciotomy (39 percent decrease), endoscopic carpal tunnel release (30 percent decrease), and mass excisions proximal to the wrist (18 percent decrease) decreased the most.

Conclusions:

From 2012 to 2017, despite a disproportionate increase in procedure charges, Medicare surgeon payment has not decreased substantially; however, total reimbursement is multifactorial and involves multiple sources of revenue and cost.
Hepatitis B surface antigen and hepatitis B RNA changes in HIV/hepatitis B virus co-infected participants receiving hepatitis B virus-active antiretroviral therapy
Authors: Hawkins Claudia , Kang Minhee , Bhattacharya Debika , Cloherty Gavin , Kuhns Mary , Matining Roy , Thio Chloe , Samaneka Wadzanai , Chinula Lameck , Mulinda Nyirenda , Badal-Faesen Sharlaa , Sugandhavesa Patcharaphan , Lama Javier , Gaseitsiwe Simani , Holzmayer Vera , Anderson Mark , Murphy Robert , Peters Marion
Published: February 2022

Introduction:

With advances in hepatitis B virus (HBV) therapies, there is a need to identify serum biomarkers that assess the HBV covalently closed circular DNA (cccDNA) reservoir and predict functional cure in HIV/HBV co-infection.

Methods:

In this retrospective study, combining samples from HIV/HBV co-infected participants enrolled in two ACTG interventional trials, proportions achieving HBsAg less than 0.05 log10 IU/ml and HBV RNA less than log10 1.65 U/ml or not detected (LLoQ/NEG) in response to DUAL [tenofovir TDF+emtricitabine (FTC)] vs. MONO [FTC or lamivudine (3TC)] HBV-active ART, were measured. Predictors of qHBsAg less than 0.05 log10 IU/ml were evaluated in logistic regression models.

Results:

There were 88 participants [58% women, median age 34; 47 on DUAL vs. 41 on MONO HBV-active ART]. Twenty-one percent achieved HBsAg less than 0.05 log10 IU/ml (30% DUAL vs. 10% MONO). Time to HBsAg less than 0.05 log10 IU/ml was lower (P 
= 0.02) and the odds of achieving HBsAg less than 0.05 log10 IU/ml were higher (P = 0.07) in DUAL participants. HBV RNA became less than LLoQ/NEG in 47% (DUAL 60% vs. MONO 33%). qHBsAg less than 3 log10 IU/ml was the strongest predictor of HBsAg less than 0.05 log10 IU/ml.

Conclusion:

This study supports current recommendations of TDF-based DUAL-HBV active ART for initial use in HIV/HBV co-infection. HBV RNA could be a useful marker of treatment response in HIV/HBV co-infected patients on HBV-active ART.
Patient-Reported Bowel, Urinary, and Sexual Outcomes After Laparoscopic-Assisted Resection or Open Resection for Rectal Cancer
Authors: Mercieca-Bebber Rebecca , Eggins Renee , Brown Kilian , Gebski Val J. , Brewer Kate , Lai Lenna , Bailey Lisa , Solomon Michael J. , Lumley John W. , Hewett Peter , Clouston Andrew D. , Wilson Kate , Hague Wendy , Hayes Julian , White Stephen , Morgan Matt , Simes R. John , Stevenson Andrew R. L.
Published: February 2022

Objective:

The aim of this study was to compare patient-reported urinary, bowel, and sexual functioning of ALaCaRT Trial participants randomized to open or laparoscopic surgery for rectal cancer.

Summary Background Data:

The primary endpoint, noninferiority of laparoscopic surgical resection adequacy, was not established.

Methods:

Participants completed QLQ-CR29 at baseline, 3, and 12 months post-surgery. Additionally, women completed Rosen’s Female Sexual Functioning Index (FSFI). Men completed the International Index of Erectile Function (IIEF) and QLQ-PR25. We compared the proportions of participants in each group who experienced moderate/severe symptoms/dysfunction at each time-point and compared mean difference scores from baseline to 12 months between groups. All analyses were intention-to-treat. Sexual functioning analyses included only the participants who expressed sexual interest at baseline.

Results:

Baseline PRO compliance of 475 randomized participants was 88%. At 12 months, a lower proportion of open surgery participants experienced moderate–severe fecal incontinence and sore skin, compared to Laparoscopic participants, and a lower proportion of men randomized to open surgery experienced moderate–severe urinary symptoms. There were no differences at 3 months for bowel or urinary symptoms. Sexual functioning among sexually interested participants was similar between groups at 3 and 12 months; however, a lower proportion of women reported moderate to severe sexual dissatisfaction at 3 months in the open as compared to the laparoscopic group, (Rebecca.mercieca@sydney.edu.au., 95% CI 0.03–0.39).

Discussion:

Despite the slightly lower proportions of open surgery participants self-reporting moderate-severe symptoms for 3 of 16 urinary/bowel domains, and lack of differences in sexual domains, it remains difficult to recommend one surgical approach over another for rectal resection.
COVID-19 onset reduced the sex ratio at birth in South Africa
Authors: Masukume Gwinyai , Ryan Margaret , Masukume Rumbidzai , Zammit Dorota , Grech Victor , Mapanga Witness
Published: February 2022

Background

The sex ratio at birth [defined as male/(male+female) live births] is anticipated to approximate 0.510 with a slight male excess. Following sudden unexpected stressful events, this ratio has been observed to decrease transiently around 3-5 months following such events. We hypothesised that stress engendered by the onset of the COVID-19 pandemic may have caused such a decrease in South Africa 3-5 months after March 2020 since in this month, South Africa reported its first COVID-19 case, death and nationwide lockdown restrictions were instituted.

Methods

We used publicly available recorded monthly live birth data from Statistics South Africa. The most recent month for which data was available publicly was December 2020. We analysed live births for a 100-month period from September 2012 to December 2020, taking seasonality into account. Chi-squared tests were applied.

Results

Over this 100-month period, there were 8,151,364 live births. The lowest recorded monthly sex ratio at birth of 0.499 was in June 2020, 3 months after March 2020. This June was the only month during this period where the sex ratio inverted i.e., fewer male live births occurred. The predicted June 2020 ratio was 0.504. The observed June 2020 decrease was statistically significant p = 0.045.

Conclusions

The sex ratio at birth decreased and inverted in South Africa in June 2020, for the first time, during the most recent 100-month period. This decline occurred 3 months after the March 2020 onset of COVID-19 in South Africa. As June 2020 is within the critical window when population stressors are known to impact the sex ratio at birth, these findings suggest that the onset of the COVID-19 pandemic engendered population stress with notable effects on pregnancy and public health in South Africa. These findings have implications for future pandemic preparedness and social policy.
SARS-CoV-2 variants of concern Alpha and Delta show increased viral load in saliva
Authors: King Kylie L. , Wilson Stevin , Napolitano Justin M. , Sell Keegan J. , Rennert Lior , Parkinson Christopher L. , Dean Delphine
Published: February 2022

Background

Higher viral loads in SARS-CoV-2 infections may be linked to more rapid spread of emerging variants of concern (VOC). Rapid detection and isolation of cases with highest viral loads, even in pre- or asymptomatic individuals, is essential for the mitigation of community outbreaks.

Methods and Findings

In this study, we analyze Ct values from 1297 SARS-CoV-2 positive patient saliva samples collected at the Clemson University testing lab in upstate South Carolina. Samples were identified as positive using RT-qPCR, and clade information was determined via whole genome sequencing at nearby commercial labs. We also obtained patient-reported information on symptoms and exposures at the time of testing. The lowest Ct values were observed among those infected with Delta (median: 22.61, IQR: 16.72-28.51), followed by Alpha (23.93, 18.36-28.49), Gamma (24.74, 18.84-30.64), and the more historic clade 20G (25.21, 20.50-29.916). There was a statistically significant difference in Ct value between Delta and all other clades (all p.adj<0.01), as well as between Alpha and 20G (p.adj<0.05). Additionally, pre- or asymptomatic patients (n=1093) showed the same statistical differences between Delta and all other clades (all p.adj<0.01); however, symptomatic patients (n=167) did not show any significant differences between clades. Our weekly testing strategy ensures that cases are caught earlier in the infection cycle, often before symptoms are present, reducing this sample size in our population.

Conclusions

COVID-19 variants Alpha and Delta have substantially higher viral loads in saliva compared to more historic clades. This trend is especially observed in individuals who are pre- or asymptomatic, which provides evidence supporting higher transmissibility and more rapid spread of emerging variants. Understanding the viral load of variants spreading within a community can inform public policy and clinical decision making.
SARS-CoV-2 IgG seroprevalence in blood donors located in three different federal states, Germany, July 2020 to June 2021 – a follow-up
Authors: Fischer Bastian , Vollmer Tanja , Knabbe Cornelius
Published: February 2022

Seroprevalence studies can contribute to better assess the actual incidence of infection. Since long-term data for Germany are lacking, we determined seroprevalence of IgG-antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,759 regular blood donors in three German federal states between July 2020 and June 2021. The IgG seroprevalence was 5.48% (95% confidence interval (CI): 4.77–6.25) overall, ranging from 5.15% (95% CI: 3.73–6.89) in Lower Saxony to 5.62% (95% CI: 4.57–6.84) in North Rhine Westphalia.
Distinct upper airway epithelium interferon-stimulated and profibrotic gene expression between adult and infant rhesus macaques infected with SARS-CoV-2
Authors: Langel Stephanie N. , Garrido Carolina , Phan Caroline , Travieso Tatianna , DeMarco Todd , Ma Zhong-Min , Reader Rachel , Olstad Katherine J. , Sammak Rebecca L. , Lakshmanappa Yashavanth Shaan , Roh Jamin W. , Watanabe Jennifer , Usachenko Jodie , Immareddy Ramya , Pollard Rachel , Iyer Smita S. , Permar Sallie , Miller Lisa A. , Van Rompay Koen K.A. , Blasi Maria
Published: February 2022

The global spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease (COVID-19) has led to a pandemic of unprecedented scale. An intriguing feature of the infection is the minimal disease in most children, a demographic at higher risk for respiratory viral diseases. To elucidate age-dependent effects of SARS-CoV-2 pathogenesis, we inoculated two rhesus macaque monkey dam-infant pairs with SARS-CoV-2 and conducted virological and transcriptomic analysis of the respiratory tract and evaluated systemic cytokine and antibody responses. Viral RNA levels in all sampled mucosal secretions were comparable across dam-infant pairs in the respiratory tract. Despite comparable viral loads, adult macaques showed higher IL-6 in serum while CXCL10 was induced in all animals. Both groups mounted neutralizing antibody (nAb) responses, with infants showing a more rapid induction at day 7. Transcriptome analysis of tracheal tissue isolated at day 14 post-infection revealed significant upregulation of multiple interferon-stimulated genes in infants compared to adults. In contrast, a profibrotic transcriptomic signature with genes associated with cilia structure and function, extracellular matrix (ECM) composition and metabolism, coagulation, angiogenesis, and hypoxia was induced in adults compared to infants. Our observations suggest age-dependent differential airway responses to SARS-CoV-2 infection that could explain the distinction in pathogenesis between infants and adults.
Probing protein ubiquitination in live cells
Authors: Qin Weihua , Steinek Clemens , Kolobynina Ksenia , Cristina Cardoso M. , Leonhardt Heinrich
Published: February 2022

The reversible attachment of ubiquitin governs the interaction, activity and degradation of proteins whereby the type and target of this conjugation determine the biological response. The investigation of this complex and multi-faceted protein ubiquitination mostly relies on painstaking biochemical analyses. Here, we employ recombinant binding domains to probe the ubiquitination of proteins in living cells. We immobilize GFP-fused proteins of interest at a distinct cellular structure and detect their ubiquitination state with red fluorescent ubiquitin binders. With this ubiquitin fluorescent three-hybrid (ubiF3H) assay we identified HP1β as a novel ubiquitination target of UHRF1. The use of linkage specific ubiquitin binding domains enabled the discrimination of K48 and K63 linked protein ubiquitination. To enhance signal-to-noise ratio, we implemented fluorescence complementation (ubiF3Hc) with split YFP. Using in addition a cell cycle marker we could show that HP1β is mostly ubiquitinated by UHRF1 during S phase and deubiquitinated by the protease USP7. With this complementation assay we could also directly detect the ubiquitination of the tumor suppressor p53 and monitor its inhibition by the anti-cancer drug Nutlin-3. Altogether, we demonstrate the utility of the ubiF3H assay to probe the ubiquitination of specific proteins and to screen for ligases, proteases and small molecules controlling this posttranslational modification.
Genome assembly of the numbat (Myrmecobius fasciatus), the only termitivorous marsupial
Authors: Peel Emma , Silver Luke , Brandies Parice , Hayakawa Takashi , Belov Katherine , Hogg Carolyn J
Published: February 2022

The numbat (Myrmecobius fasciatus) is a critically endangered Australian marsupial, and the last surviving member of the Myrmecobiidae family. The numbat regularly undergoes torpor and is unique amongst marsupials as it is the only diurnal and termitivorous species. Here we sequenced the first draft genome of the numbat using 10× Genomics chromium linked-read technology, resulting in a 3.42 Gbp genome with a scaffold N50 of 223 Kbp. A global transcriptome from liver, lung and tongue was also generated to aid genome annotation with Fgenesh++, identifying 21,465 protein-coding genes and 78.7% complete mammalian BUSCOs. To investigate adaptation to the numbat’s termitivorous diet and arid/semi-arid range, we interrogated the most highly expressed transcripts within the tongue and manually annotated taste, vomeronasal and aquaporin gene families. Antimicrobial proteins and proteins involved in digestion were highly expressed in the tongue, as expected. Similarly, umami taste receptors were also expressed in the tongue, however sweet taste receptors were not expressed in this tissue. This pattern of taste receptor expression, combined with the putative contraction of the bitter taste receptor gene repertoire in the numbat genome, may indicate a potential evolutionary adaptation to their specialized termitivorous diet. Vomeronasal and aquaporin gene repertoires were similar to other marsupials and have not undergone expansion or contraction. The draft numbat genome is a valuable tool for conservation and can be applied to population genetics/genomics studies and to investigate the unique biology of this interesting species.
SMN promotes mitochondrial metabolic maturation during myogenesis by regulating the MYOD-miRNA axis
Authors: Ikenaka Akihiro , Kitagawa Yohko , Yoshida Michiko , Lin Chuang-Yu , Niwa Akira , Nakahata Tatsutoshi , Saito Megumu K.
Published: February 2022

Spinal muscular atrophy (SMA) is a congenital neuromuscular disease caused by the mutation or deletion of survival motor neuron 1 (SMN1) gene. Although the primary cause of progressive muscle atrophy in SMA has classically been considered the degeneration of motor neurons, recent studies have indicated a skeletal muscle-specific pathological phenotype such as impaired mitochondrial function and enhanced cell death. Here we found that the downregulation of SMN causes mitochondrial dysfunction and subsequent cell death in in vitro models of skeletal myogenesis with both a murine C2C12 cell line and human induced pluripotent stem cells. During myogenesis, SMN binds to the genome upstream of the transcriptional start sites of MYOD1 and microRNA (miR)-1 and -206. Accordingly, the loss of SMN downregulates these miRs, whereas supplementation of the miRs recovers the mitochondrial function, cell survival and myotube formation of SMN-deficient C2C12, indicating the SMN-miR axis is essential for myogenic metabolic maturation. Additionally, introduction of the miRs into ex vivo muscle stem cells derived from Δ7-SMA mice caused myotube formation and muscle contraction. In conclusion, our data revealed novel transcriptional roles of SMN during myogenesis, providing an alternative muscle-oriented therapeutic strategy for SMA patients.

Highlights

Reduced SMN causes mitochondrial dysregulation in myogenic cells.

Reduced SMN downregulates miR-1 and miR-206 expression in myogenic cells.

SMN protein binds to the genome upstream of MYOD1, miR-1 and miR-206.

miR-1 and miR-206 are sufficient to improve skeletal muscle function in an SMA model.
Evaluation of international guidance for the community treatment of complex emotional needs: A systematic review
Authors: Zhan Yuen Nicholas Wong , Barnett Phoebe , Rains Luke Sheridan , Johnson Sonia , Billings Jo
Published: February 2022

Background

Guidelines for the treatment and management of “personality disorder” were introduced to provide guidance on best practice from evidence and views of key stakeholders. However, this guidance varies as there is yet to be an overall, internationally recognised consensus on the best mental health care for people with complex emotional needs (CEN - our preferred working term for the needs of people using services for or related to “personality disorder”).

Aims

We aimed to identify and synthesise recommendations made by different mental health organisations from across the world on community treatment for people with CEN.

Methods

This systematic review consisted of three stages: 1. systematic literature and guideline search, 2. quality appraisal, and 3. data synthesis. We combined a search strategy involving both systematic searching of bibliographic databases and supplementary search methods of grey literature. Key informants were also contacted to further identify relevant guidelines. Codebook thematic analysis was then conducted. The quality of all included guidelines was assessed and considered alongside results.

Results

After synthesising 29 guidelines from 11 countries and 1 international organisation, we identified four main domains, with a total of 27 themes. Important key principles on which there was consensus included continuity of care, equity of access, accessibility of services, availability of specialist care, taking a whole systems approach, trauma informed approaches, and collaborative care planning and decision making.

Conclusions

Existing international guidelines shared consensus on a set of principles for the community treatment of CEN. However, half of the guidelines were of lower methodological quality, with many recommendations not backed by evidence.