bluuebunny/crossref_metadata_2025 huggingface dataset:
Moralized language predicts hate speech on social media
Authors: Solovev Kirill , Pröllochs Nicolas
Published: December 2022

Hate speech on social media threatens the mental health of its victims and poses severe safety risks to modern societies. Yet, the mechanisms underlying its proliferation, though critical, have remained largely unresolved. In this work, we hypothesize that moralized language predicts the proliferation of hate speech on social media. To test this hypothesis, we collected three datasets consisting of N = 691,234 social media posts and ∼35.5 million corresponding replies from Twitter that have been authored by societal leaders across three domains (politics, news media, and activism). Subsequently, we used textual analysis and machine learning to analyze whether moralized language carried in source tweets is linked to differences in the prevalence of hate speech in the corresponding replies. Across all three datasets, we consistently observed that higher frequencies of moral and moral-emotional words predict a higher likelihood of receiving hate speech. On average, each additional moral word was associated with between 10.76% and 16.48% higher odds of receiving hate speech. Likewise, each additional moral-emotional word increased the odds of receiving hate speech by between 9.35 and 20.63%. Furthermore, moralized language was a robust out-of-sample predictor of hate speech. These results shed new light on the antecedents of hate speech and may help to inform measures to curb its spread on social media.
Theory of transformation-mediated twinning
Authors: Lu Song , Sun Xun , Tian Yanzhong , An Xianghai , Li Wei , Chen Yujie , Zhang Hualei , Vitos Levente
Published: December 2022

High-density and nanosized deformation twins in face-centered cubic (fcc) materials can effectively improve the combination of strength and ductility. However, the microscopic dislocation mechanisms enabling a high twinnability remain elusive. Twinning usually occurs via continuous nucleation and gliding of twinning partial dislocations on consecutive close-packed atomic planes. Here we unveil a completely different twinning mechanism being active in metastable fcc materials. The transformation-mediated twinning (TMT) is featured by a preceding displacive transformation from the fcc phase to the hexagonal close-packed (hcp) one, followed by a second-step transformation from the hcp phase to the fcc twin. The nucleation of the intermediate hcp phase is driven by the thermodynamic instability and the negative stacking fault energy of the metastable fcc phase. The intermediate hcp structure is characterized by the easy slips of Shockley partial dislocations on the basal planes, which leads to both fcc and fcc twin platelets during deformation, creating more twin boundaries and further enhancing the prosperity of twins. The disclosed fundamental understanding of the complex dislocation mechanism of deformation twinning in metastable alloys paves the road to design novel materials with outstanding mechanical properties.
On the interplay of hierarchies, conflicts, and cooperation: An experimental approach
Authors: Lozano Pablo , Antonioni Alberto , Sánchez Angel
Published: December 2022

Previous research suggests that it is difficult to maintain cooperation in a large society when there is a strong hierarchical structure. In this study, we implement online human experiments to study the effects of exogenous variation in a particular notion of hierarchy on cooperation and conflict within groups. We demonstrate how cooperation can be maintained when collective action is accompanied by dyadic conflicts whose outcome feeds back on the hierarchical rank of the contestants. We find that the majority of individuals take part in conflicts and that highly ranked individuals mostly cooperate and engage in conflicts as a way to punish noncooperators. As a consequence, stable hierarchical groups can arise and maintain high levels of cooperation. Our results are in agreement with the prediction of earlier theoretical models on hierarchical societies and are relevant to understanding the interplay of hierarchy, cooperation, and conflict.
Continuum level density calculated under the absorbing boundary condition
Authors: Maeda T , Taniguchi Y , Fumimoto T , Nakamoto R , Ito M
Published: December 2022

We have applied an absorbing boundary condition (ABC) method to calculations of the level density (LD) and the continuum level density (CLD). The results of LD and CLD in the ABC calculation are compared with those calculated by the complex scaling method (CSM). The energy dependences of LD in ABC show similar behavior to those in CSM around the resonance energy but they are prominently different, especially at the lower-energy region, due to the different sequence of the energy eigenvalues in the complex plane. The phase shift for two-body scattering problems is also derived from CLD. The phase shift obtained by ABC is almost the same as that calculated from CSM although the ABC method seems to be slightly inferior to the CSM calculation in the numerical precision. The improvement of the numerical precision in ABC is also discussed.
Development of ultra-pure gadolinium sulfate for the Super-Kamiokande gadolinium project
Authors: Hosokawa K , Ikeda M , Okada T , Sekiya H , Fernández P , Labarga L , Bandac I , Perez J , Ito S , Harada M , Koshio Y , Thiesse M D , Thompson L F , Scovell P R , Meehan E , Ichimura K , Kishimoto Y , Nakajima Y , Vagins M R , Ito H , Takaku Y , Tanaka Y , Yamaguchi Y
Published: December 2022

This paper reports the development and detailed properties of about 13 metric tons of gadolinium sulfate octahydrate, $\rm Gd_2(\rm SO_4)_3\cdot \rm 8H_2O$, which has been dissolved into Super-Kamiokande (SK) in the summer of 2020. We evaluate the impact of radioactive impurities in $\rm Gd_2(\rm SO_4)_3\cdot \rm 8H_2O$ on diffuse supernova neutrino background searches and solar neutrino observation and confirm the need to reduce radioactive and fluorescent impurities by about three orders of magnitude from commercially available high-purity $\rm Gd_2(\rm SO_4)_3\cdot \rm 8H_2O$. In order to produce ultra-high-purity $\rm Gd_2(\rm SO_4)_3\cdot \rm 8H_2O$, we have developed a method to remove impurities from gadolinium oxide, Gd2O3, consisting of acid dissolution, solvent extraction, and pH control processes, followed by a high-purity sulfation process. All of the produced ultra-high-purity $\rm Gd_2(\rm SO_4)_3\cdot \rm 8H_2O$ is assayed by inductively coupled plasma mass spectrometry and high-purity germanium detectors to evaluate its quality. Because of the long measurement time of high-purity germanium detectors, we have employed several underground laboratories for making parallel measurements including the Laboratorio Subterráneo de Canfranc in Spain, Boulby in the UK, and Kamioka in Japan. In the first half of production, the measured batch purities were found to be consistent with the specifications. However, in the latter half, the $\rm Gd_2(\rm SO_4)_3\cdot \rm 8H_2O$ contained one order of magnitude more 228Ra than the budgeted mean contamination. This was correlated with the corresponding characteristics of the raw material Gd2O3, in which an intrinsically large contamination was present. Based on their modest impact on SK physics, they were nevertheless introduced into the detector. To reduce 228Ra for the next stage of gadolinium loading to SK, a new process has been successfully established.
Inhalable microparticles as drug delivery systems to the lungs in a dry powder formulations
Authors: Knap Karolina , Kwiecień Konrad , Reczyńska-Kolman Katarzyna , Pamuła Elżbieta
Published: December 2022

Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases. Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution, leading to a more effective therapy with reduced required doses and side effects. On the other hand, there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical, aerodynamic and biological properties, which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result. Therefore, we focused on powders consisting of polysaccharides, lipids, proteins or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers. We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms. This review article addresses the most common manufacturing methods with novel modifications, pros and cons of different materials, drug loading capacities with release profiles, and biological properties such as cytocompatibility, bactericidal or anticancer properties.
Digging into the Lettuce Cold-Specific Root Microbiome in Search of Chilling Stress Tolerance-Conferring Plant-Growth-Promoting Bacteria
Authors: Persyn Antoine , Méndez Sonia García , De Meyer Sam , Beirinckx Stien , Willems Anne , De Tender Caroline , Goormachtig Sofie
Published: December 2022

Growth of lettuce ( Lactuca sativa) is severely hampered by low temperatures, even when cultivated under greenhouse conditions. Root-associated bacteria might promote plant growth under stressful conditions. Therefore, we analyzed the effect of low temperatures on the lettuce root-associated microbiome to evaluate whether microbiome-based selection aids in identiying bacteria that stimulate plant growth in the cold. 16S ribosomal RNA gene amplicon sequencing was used to examine the compositional differences in the lettuce root-associated microbiome when grown under low- and control-temperature conditions. Chilling temperatures significantly altered the lettuce root endosphere composition, whereas their effects were less severe in the rhizosphere and absent in the bulk soil. Several cold-enriched families were found in both the rhizosphere and the root endosphere, nine of which were Oxalobacteraceae, Pseudomonadaceae, Flavobacteriaceae, Microscillaceae, Sphingobacteriaceae, Comamonadaceae, Devosiaceae, Methylophilaceae and env.OPS_17. Concurrently, a collection of lettuce root-colonizing bacteria was established and, based on correlation with these families, representative isolates were screened. None of the lettuce root isolates showed growth-promoting effects but three growth-promoting Flavobacterium strains from an available collection of grass root-colonizing bacteria were identified. Amplicon sequence variant (ASV) annotation of the lettuce and grass strains revealed that strains matching cold-enriched or highly abundant ASVs in at least one soil promoted growth in the cold. Overall, our data demonstrate that microbiome analyses, combined with high-throughput bacterial isolations might be a helpful tool to isolate effective cold growth-promoting strains.
A Frontline, Rapid, Nucleic Acid-Based Fusarium circinatum Detection System Using CRISPR/Cas12a Combined with Recombinase Polymerase Amplification
Authors: Chen Zhenpeng , Yang Xiao , Xia Hongming , Wu Cuiping , Yang Jing , Dai Tingting
Published: December 2022

Pitch canker caused by the fungus Fusarium circinatum is a damaging disease that affects pines in Europe, South Africa, and North America in both the southeast and west coast of the United States. Several countries, including China, have listed F. circinatum as a quarantine pathogen. Timely detection, an important pillar of the quarantine effort, can efficiently prevent the introduction of F. circinatum into new areas or facilitate management and eradication strategies in already infested sites. In this study, we developed an F. circinatum detection technique based on a combination of recombinase polymerase amplification (RPA) with CRISPR/Cas12a technology (termed RPA-CRISPR/Cas12a). After obtaining DNA, this novel method can be utilized for the molecular identification of F. circinatum using the naked eye and can specifically detect F. circinatum at DNA concentrations as low as 200 fg within 30 min at 37°C. The system is sensitive for both standard laboratory samples and samples from the field. In summary, we have developed a simple, rapid, sensitive, unaided-eye visualization, RPA-CRISPR/Cas12a-based detection system for the molecular identification of F. circinatum that does not require technical expertise or expensive ancillary equipment.
Effect of Enteral Guanfacine on Dexmedetomidine Use in the ICU
Authors: Fetters Megan B. , Diep Calvin , Ran Ran , Kloosterboer Amy
Published: December 2022

OBJECTIVES:

Describe the efficacy and safety of guanfacine for dexmedetomidine weaning in critically ill patients.

DESIGN:

Retrospective descriptive analysis.

SETTING:

Six hundred thirteen–bed academic medical center from October 2020 to October 2021.

PATIENT/SUBJECTS:

All Adult patients on IV dexmedetomidine who received at least one dose of guanfacine for sedation or agitation were included.

INTERVENTIONS:

Enteral guanfacine.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was discontinuation of dexmedetomidine therapy within 48 hours after guanfacine initiation. Secondary outcomes assessed included adjunctive medication use, rate of dexmedetomidine reinitiation, and safety outcomes. One hundred five patients were included in the analysis. Median age was 59 years old, 66% were male, and median daily dose of guanfacine was 1.5 mg. Dexmedetomidine was discontinued within 48 hours in 58% of patients (n = 61) and within 72 hours in 71% of patients (n = 75). Fifty-five percent of patients (n = 58) required rescue medications for poorly controlled agitation, sedation, or pain while on guanfacine. Dexmedetomidine withdrawal occurred in 2% of patients (n = 2) while on guanfacine. Adverse effects attributed to guanfacine occurred in 8% of patients (n = 8), all experiencing hypotension leading to medication discontinuation.

CONCLUSION:

Dexmedetomidine was successfully weaned within 48 hours of guanfacine initiation in 58% of patients with minimal withdrawal or adverse effects. Guanfacine may be an effective and safe enteral option for dexmedetomidine weaning in critically ill patients.
Academic and Community ICUs Participating in a Critical Care Randomized Trial: A Comparison of Patient Characteristics and Trial Metrics
Authors: Tsang Jennifer L. Y. , Binnie Alexandra , Duan Erick H. , Johnstone Jennie , Heels-Ansdell Diane , Reeve Brenda , Trop Sebastien , Hosek Paul , Dionne Joanna C. , Archambault Patrick , Lysecki Paul , Cirone Robert , Zytaruk Nicole L. , Dechert William , Camargo Mercedes Peñuela , Jesso Rebecca , McMillan Elliot , Panchbhaya Zaynab , Campbell Tracy , Saunders Lois , Copland Mary , Kavikondala Kanthi , Cook Deborah J. ,   for the Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT) Investigators and the Canadian Critical Care Trials Group
Published: December 2022

OBJECTIVES:

Clinical research in Canada is conducted primarily in “academic” hospitals, whereas most clinical care is provided in “community” hospitals. The objective of this nested observational study was to compare patient characteristics, outcomes, process-of-care variables, and trial metrics for patients enrolled in a large randomized controlled trial who were admitted to academic and community hospitals in Canada.

DESIGN:

We conducted a preplanned observational study nested within the Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT, a randomized controlled trial comparing probiotics to placebo in mechanically ventilated patients) Research Program.

SETTING:

ICUs.

PATIENTS:

Mechanically ventilated patients.

MEASUREMENTS:

We compared patient characteristics, interventions, outcomes, and trial metrics between patients enrolled in PROSPECT from academic and community hospitals.

MAIN RESULTS:

Participating centers included 34 (82.9%) academic and seven (17.1%) community hospitals, which enrolled 2,203 (86.2%) and 352 (13.8%) patients, respectively. Compared with academic hospitals, patients enrolled in community hospitals were older (mean [sd] 62.7 yr [14.9 yr] vs 59.5 yr [16.4 yr]; p = 0.044), had longer ICU stays (median [interquartile range {IQR}], 13 d [8–23 d] vs 11 d [7–8 d]; p = 0.012) and higher mortality (percentage, [95% CI] in the ICU, 30.4% [25.8–35.4%]vs 20.5% [18.9–11.3%]; p = 0.002) and hospital (40.6% [35.6–45.8%] vs 26.1% [24.3–27.9%]; p < 0.001). Trial metrics, including informed consent rate (85.9% vs 76.3%; p = 0.149), mean (sd) monthly enrolment rate (2.1 [1.4] vs 1.1 [0.7]; p = 0.119), and protocol adherence (90.6% vs 91.6%; p = 0.207), were similar between community and academic ICUs.

CONCLUSIONS:

Community hospitals can conduct high-quality research, with similar trial metrics to academic hospitals. Patient characteristics differed between community and academic hospitals, highlighting the need for broader engagement of community hospitals in clinical research to ensure generalizability of study results.
Early Empiric Antibiotic Treatment Among Neonates With Congenital Heart Defects: A Brief Report of an Integrative Review
Authors: Davis Jessica A. , Ho Rebecca , Pace Elizabeth K. , Kim Audrey , Lin Jiuann-Huey , Morowitz Michael J.
Published: December 2022

OBJECTIVES:

Despite improved rates of survival, neonates with congenital heart defects experience serious comorbidities. Antibiotics are used widely in other critically ill neonates, and exposure in the first 7 days after birth (early empiric antibiotic treatment) has been associated with increased risk of adverse outcomes. The purpose of this brief report is to summarize and evaluate existing evidence pertaining to early empiric antibiotic treatment and associations with adverse outcomes among neonates with congenital heart defects.

DESIGN:

An integrative review of the literature was performed.

SETTING:

The search was conducted in PubMed and Ovid Medline, and Global Health databases. Medical Subject Headings terms and Boolean phrases were used.

SUBJECTS:

Original research articles were included if the study cohort neonates with congenital heart defects, were published in English, and included a description or evaluation of early empiric antibiotic treatment in the first 28 days of life. Endocarditis and postoperative antibiotic prophylaxis investigations were excluded.

MAIN RESULTS:

Our search generated 249 articles. Search results were listed in an Excel spreadsheet and screened by four authors. Articles that did not pertain to the population of interest were excluded. Fourteen articles were included in the full-text review. Data from these articles were summarized in a table and evaluated by all authors. No articles were found discussing early empiric antibiotic treatment in neonates with congenital heart defects.

LIMITATIONS:

Our search generated no results, impairing our ability to fulfill the purpose of the brief report.

CONCLUSIONS:

There have been no studies regarding early empiric antibiotic treatment among neonates with congenital heart defects. Research is needed to understand the prevalence, indications, and potential consequences of early empiric antibiotic treatment in this population.
Characterization of a Thermoacoustic-based Pulsed High Power Microwave Detector Chain
Authors: Frey James J. , Barnes Ronald A. , McClory John W.
Published: December 2022

Detection of microwave-induced thermoacoustic (TA) wave generation was evaluated as a potential technique for detection of high power microwave (HPM) directed energy exposure. Even when HPM is employed for counter-materiel effects, incidental but still potentially harmful personnel exposure is possible. Real-time detection of ongoing exposure with potentially unknown time and frequency domain characteristics is a critical first step in preventing acute health effects by alerting and then enabling the timely use of electromagnetic frequency energy shielding, such as structures and vehicles. Leveraging the TA effect as a field interaction mechanism, a lossy dielectric polymer subjected to pulsed HPM was tested using a planar sample geometry with thin film piezoelectric sensors used to capture the resulting TA output. The piezoelectric signal was analyzed in both the time and frequency domain to determine empirical relationships between incident microwave beam properties and signal components. This analysis was coupled with an empirically-based single term Cole-Cole model approximation fit for the complex permittivity. The results were used to identify appropriate signal conditioning and processing techniques needed to convert the TA response into a useful form for personnel exposure applications. These results also served as a comparison point for multi-physics finite element method computational modeling of the electromagnetic response of a simplified three-layer tissue model.
IgA nephropathy pathogenesis and therapy: Review & updates
Authors: Habas Elmukhtar , Ali Elrazi , Farfar Khalifa , Errayes Mahdi , Alfitori Jamal , Habas Eshrak , Ghazouani Hafedh , Akbar Raza , Khan Fahim , Al Dab Aisha , Elzouki Abdel-Naser
Published: December 2022

Background:

IgA nephropathy (IgAN) is the most frequent type of primary glomerulonephritis since the first type was described more than four decades ago. It is the prevalent cause of primary glomerular disease that causes end-stage renal disease. In most patients with IgAN, hematuria is the most common reported symptom, particularly in those with a preceding upper respiratory tract infection. Although the pathogenesis of IgAN is usually multifactorial, autoimmune complex formation and inflammatory processes are the most widely recognized pathogenic mechanisms. Multiple approaches have been trialed as a therapy for IgAN, including tonsillectomy, steroids, other immune-suppressive therapy in different regimens, and kidney transplantation.

Aim and method:

PubMed, Google, Google Scholar, Scopus, and EMBASE were searched by the authors using different texts, keywords, and phrases. A non-systemic clinical review is intended to review the available data and clinical updates about the possible mechanism(s) of IgAN pathogenesis and treatments.

Conclusion:

IgAN has a heterogeneous pattern worldwide, making it difficult to understand its pathogenesis and treatment. Proteinuria is the best guide to follow up on the IgAN progression and treatment response. Steroids are the cornerstone of IgAN therapy; however, other immune-suppressive and immune-modulative agents are used with a variable response rate. Kidney transplantation is highly advisable for IgAN patients, although the recurrence rate is high. Finally, IgAN management requires collaborative work between patients and their treating physicians for safe long-term outcomes.
Analysis of the potential molecular biology of triptolide in the treatment of diabetic nephropathy: A narrative review
Authors: Gao Ying , Guo Zhaoan , Liu Yingying
Published: December 2022

Objective:

To explore the potential mechanism of triptolide in diabetic nephropathy (DN) treatment using network pharmacology.

Methods:

The main targets of triptolide were screened using the TCMSP, DrugBank, and NCBI databases, and gene targets of DN were searched using the DrugBank, DisGeNET, TTD, and OMIM databases. All of the above targets were normalized using the UniProt database to obtain the co-acting genes. The co-acting genes were uploaded to the STRING platform to build a protein-protein interaction network and screen the core acting targets. Gene ontology and Kyoto encyclopedia of genes and genomes analyses of the core targets were performed using Metascape. Molecular docking validation of triptolide with the co-acting genes was performed using the Swiss Dock platform.

Results:

We identified 76 potential target points for triptolide, 693 target points for DN-related diseases, and 24 co-acting genes. The main pathways and biological processes involved are lipids and atherosclerosis, IL-18 signaling pathway, TWEAK signaling pathway, response to oxidative stress, hematopoietic function, and negative regulation of cell differentiation. Both triptolide and the active site of the core target genes can form more than 2 hydrogen bonds, and the bond energy is less than -5kJ/mol. Bioinformatics analysis showed that triptolide had a regulatory effect on most of the core target genes that are aberrantly expressed in DKD.

Conclusion:

Triptolide may regulate the body’s response to cytokines, hormones, oxidative stress, and apoptosis signaling pathways in DN treatment by down-regulating Casp3, Casp8, PTEN, GSA3B and up-regulating ESR1, and so forth.
Renal diseases associated with multiple sclerosis: A narrative review
Authors: Alugba Gabriel , Urhi Alexsandra , Olateju Iyanu Victoria , Onyemarin Henry , Uzzi Consolata , Oshiba-Fowode Tolulope , Obomanu Elvis , Popoola Hakeem Adegboyega , Okoronkwo Emeka J. , Ukenenye Emmanuel , Asaolu Gideon , Oladunjoye Adeolu Funso , Oladunjoye Olubunmi
Published: December 2022

The mechanisms of renal pathology in multiple sclerosis (MS) can be related to the disease itself or its treatment. Although kidney disease can be associated with MS, not much has been reported in the literature; hence, our study aimed to describe the prevalence and types of renal diseases and discuss their prognosis in patients with MS. A literature search (2012–2022) was performed using the Scale for the Assessment of Narrative Review Articles. The databases searched included MEDLINE (PubMed) and EMBASE. Fourteen articles from these databases met the inclusion criteria. The inclusion criteria were as follows: publications with full-text access. Articles published in English. Original articles related to renal diseases in MS. The prevalence of renal diseases in MS from the articles obtained ranged from 0.74% to 2.49%. Interferon beta (IFN-β)-associated glomerulonephritis was common among the reviewed articles. Significant improvement and resolution of the pathology were observed after the discontinuation of the offending medication. Renal symptoms in 2 out of 4 cases with renal thrombotic microangiopathy (TMA) induced by interferon-beta progressed to chronic kidney disease, even after the drug was stopped. Other studied renal pathologies included nephrolithiasis secondary to urinary retention and urinary catheter use in patients with MS.
Efficacy and safety of 400 mg efavirenz versus standard 600 mg dose when taken with tenofovir and lamivudine combination in Indian adult patients with HIV-1 infection: An open-label, interventional, randomized, non-inferiority trial
Authors: Dravid Ameet , Pilawan Anant S. , S. Anuradha , Morkar Dnyanesh N. , Ramapuram John T , Madhukarrao Kulkarni Milind , Naik K. Sunil , Bhrusundi Milind , K. R Raveendra , Nageswaramma Siddabathuni , Kulkarni Vinay
Published: December 2022

Background:

To evaluate the non-inferiority of low dose efavirenz (400 mg) to standard dose efavirenz (600 mg), when taken in combination with tenofovir and lamivudine in Indian patients with HIV-1 infection.

Methods:

An open-label, interventional phase IV study with blinded assessment was conducted across 17 sites in India. HIV-1-infected antiretroviral therapy-naive adult patients (≥18 years of age) with a plasma HIV-1 viral load of at least 1000 copies per mL were randomized to receive either tenofovir/lamivudine/efavirenz (TLE) 400 or TLE 600. The primary endpoint was the difference in the proportion of patients achieving < 200 copies per mL at the end of 24 weeks.

Results:

A total of 265 patients were enrolled and were randomized in 1:1 ratio to TLE 400 group (130 patients) and TLE 600 group (135 patients). At week 24, the proportion of patients with a viral load of less than 200 copies per mL was 80.70% for TLE 400 and 78.95% for TLE 600 (difference 1.75%, 90% confidence interval: −7.01, 10.49) which was within the predefined margin of −10% (90% confidence interval). Significantly lower study drug-related adverse events were observed in TLE 400 group compared to TLE 600 group (52.30%, n = 68 vs 64.92%, n = 87; P = .037). The treatment discontinuation percentage was marginally higher by 2.08% in TLE 600 group.

Conclusion:

The fixed-dose combination of TLE 400 is non-inferior to TLE 600 in terms of viral suppression and has an improved safety profile over 24 weeks in adult Indian patients with HIV-1 infection.
Two-year follow-up of a young male with possible acute hemorrhagic leukoencephalitis: A case report
Authors: Wu Chen , Zhang Weiliang , Jiao Yan , Dong Minhui , Zhou Heng , Lv Yun , Yang Jun
Published: December 2022

Rationale:

Acute hemorrhagic leukoencephalitis (AHLE) is a rare but fetal fulminant demyelinating disease of unknown etiology. It is commonly regarded as a severe variant of acute demyelinating encephalomyelitis (ADEM). Its rapid clinical deterioration and high mortality appeal to clinicians to attach importance to early diagnosis. Immunosuppressive therapy is the main management to attenuate the autoimmune process, but with varied response and prognosis.

Patient concerns:

A young male presented with moderate fever, headache and seizures after extraction of impacted teeth, and then deteriorated rapidly to deep coma. Initial magnetic resonance imaging (MRI) revealed multiple plaque-like lesions in bilateral cerebra, right thalamus and pontobulbar region with massive edematous swelling and multifocal small hemorrhagic foci. Inflammatory parameters in the peripheral blood were only mild higher with a pleocytosis in CSF.

Diagnosis:

His clinical presentation, laboratory evaluation and radiological features were consistent with a suspected diagnosis of AHLE.

Interventions:

He underwent pulse corticosteroids initially but failed to respond to it. However, his consciousness improved obviously when he was treated with multiple courses of intravenous injection of immunoglobulin (IVIG) combined with mycophenolate mofetil (MMF).

Outcomes:

The patient regained consciousness gradually on day 180 and was in minimally conscious state (MCS) during the two-year follow-up.

Lessons:

AHLE presents distinctly from classical ADEM, and the situation may pose a diagnostic challenge. Clinicians should be vigilant in recognizing AHLE because of its rapid clinical deterioration and high mortality. We highlight the critical role of multimodal MRI, particularly susceptibility-weighted imaging (SWI) in the diagnosis of AHLE if cerebral biopsies are unavailable. Multiple courses of IVIG with MMF may be effective when early single pulse of corticosteroids fails. Individual who survives the initial insult may carry relatively good prognosis.
Treatment of heterotopic cervical pregnancy by ultrasound-guided hysteroscopy: A case report and literature review
Authors: Sheng Shuman , Zhang Haomeng , Pan Zhengwu , Li Tao , Wang Xin , Shi Min , Wang Fei
Published: December 2022

Background:

Heterotopic cervical pregnancy is a rare event of ectopic pregnancy with an incidence rate of < 1%. Herein, we report a rare case of successful treatment of heterotopic pregnancy following an in vitro fertilization-embryo transfer using ultrasound-guided hysteroscopy. In order to choose the best treatment option, we reviewed the clinical treatments and discussion of heterotopic cervical pregnancy over the last 15 years.

Methods:

The heterotopic pregnancy was terminated using ultrasound-guided hysteroscopy; however, the intrauterine pregnancy was maintained. We searched for the keywords “cervical pregnancy combined with intrauterine pregnancy,” “compound pregnancy,” “assisted reproductive technology,” “cervical pregnancy,” and “ectopic pregnancy” on PubMed to include articles published in the last 15 years.

Results:

The patient underwent an emergency cervical cerclage at 22 weeks’ gestation for cervical insufficiency and delivered a healthy newborn at 38 weeks’ gestation by transvaginal compliance. Twenty-one relevant case reports were selected. After analysis and discussion, we found that assisted reproductive technology is more likely to lead to heterotopic pregnancy than unassisted reproduction. Most women requesting the preservation of intrauterine embryos opted for surgical termination of cervical pregnancy and achieved the ideal outcomes.

Conclusion:

More attention should be paid to the diagnosis and treatment of heterotopic pregnancies to obtain the most optimal pregnancy outcome and long-term prognosis. Hysteroscopic surgery is a completely feasible cervical pregnancy treatment option with less postoperative impact on the mother and the intrauterine fetus.
The Physiatrist’s Guide to Cyclist Palsy: A Narrative Review
Authors: Farag Jordan , Sherwood David , Kuwabara Anne , Kumbhare Dinesh
Published: December 2022

Ulnar neuropathy at the wrist is a common consequence of long-duration cycling, a condition termed ‘Cyclist Palsy’. Although Cyclist Palsy has been clinically well-described in the literature, a gap exists regarding its electrodiagnostic evaluation and management. Patients with Cyclist Palsy present with a wide variety of sensory or motor impairments, depending on the location of the lesion. Electrodiagnostic studies are essential for accurate localization, with studies suggesting that pure motor lesions sparing the hypothenar muscles are most common among cyclists. This paper aims to provide the electromyographer and physiatrist with a clinical approach to Cyclist Palsy, and management strategies including patient education, equipment changes, and alterations to bicycle fit.
Fostering integration among students with different backgrounds using an orthotic community service program
Authors: Hassan Beygi Babak , Wang Kubert Tianghang , Chan Hiu Lam , Wu Hui Dong , Hung Percy Ho Tim , So Mike Ka Pui , Kwong Theresa , Wong Man Sang
Published: December 2022

Background:

In this globalization era, institutions are developing strategies including international service-learning pedagogies to integrate global perspectives and dimensions into the learning and teaching processes to develop students' capacity in intercultural competence.

Objective:

This study aimed to assess the students' intercultural learning outcome through provision of orthotic community service to the less-privileged children.

Methods:

A Hong Kong–based university collaborated with 2 American universities to conduct an orthotic community service program for the children with cerebral palsy in mainland China. In the process of service delivery, the students with different backgrounds worked closely and students' professional knowledge, intercultural understanding, and communication skills were evaluated. A mixed-method approach was adopted to investigate on how this international program could facilitate meaningful interactions in clinical practices. Preprogram and postprogram surveys and focus group interviews were conducted. Statistical analyses were performed on the quantitative data, while interview data were analyzed thematically.

Results:

A comparison of preprogram and postprogram surveys showed that the students perceived this community service program important for enhancement of their capabilities to communicate with people from other cultures (n = 39, p < 0.05). It also showed an increase in local students' willingness to work with people from other cultures. Some themes related to intercultural competences were identified from the interview: “intercultural awareness, understanding, and communication” as well as openness to work/socialize with people from other cultures.”

Conclusions:

This study demonstrated that an international community service program could initiate positive changes in students' intercultural communication capability and interest to work with culturally different people.
T-cell responses induced by ChAdOx1 nCoV-19 (AZD1222) vaccine to wild-type severe acute respiratory syndrome coronavirus 2 among people with and without HIV in South Africa
Authors: McMahon William C. , Kwatra Gaurav , Izu Alane , Koen Anthonet L. , Greffrath Johann , Fairlie Lee , Patel Faeezah , Mukendi Christian K. , Mbele Nkululeko J. , Lala Rushil , Burgers Wendy A. , Nunes Marta C. , Cutland Clare L. , Gilbert Sarah C. , Lambe Teresa , Pollard Andrew J. , Madhi Shabir A.
Published: December 2022

Objective(s):

This study aimed to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell responses 14 days after single-dose ChAdOx1 nCoV-19 (AZD1222) vaccination in black Africans with and without HIV in South Africa, as well as determine the effect of AZD1222 vaccination on cell-mediated immune responses in people with HIV (PWH) with prior SARS-CoV-2 infection.

Methods:

A total of 70 HIV-uninfected people and 104 PWH were prospectively enrolled in the multicentre, randomized, double-blinded, placebo-controlled, phase Ib/IIa trial (COV005). Peripheral blood mononuclear cells (PBMCs) were collected from trial participants 14 days after receipt of first dose of study treatment (placebo or AZD1222 vaccine). T-cell responses against the full-length spike (FLS) glycoprotein of wild-type SARS-CoV-2 and mutated S-protein regions found in the Alpha, Beta and Delta variants were assessed using an ex-vivo ELISpot assay.

Results:

Among AZD1222 recipients without preceding SARS-CoV-2 infection, T-cell responses to FLS of wild-type SARS-CoV-2 were similarly common in PWH and HIV-uninfected people (30/33, 90.9% vs. 16/21, 76.2%; P = 0.138); and magnitude of response was similar among responders (78 vs. 56 SFCs/106 PBMCs; P = 0.255). Among PWH, AZD1222 vaccinees with prior SARS-CoV-2 infection, displayed a heightened T-cell response magnitude compared with those without prior infection (186 vs. 78 SFCs/106 PBMCs; P = 0.001); and similar response rate (14/14, 100% vs. 30/33, 90.9%; P = 0.244).

Conclusion:

Our results indicate comparable T-cell responses following AZD1222 vaccination in HIV-uninfected people and PWH on stable antiretroviral therapy. Our results additionally show that hybrid immunity acquired through SARS-CoV-2 infection and AZD1222 vaccination, induce a heightened T-cell response.
Position Statement: Vitamin D Intake to Prevent Osteoporosis and Fracture in Adults
Authors: Han Anna , Park Yongsoon , Lee Young-Kyun , Park So Young , Park Clara Yongjoo
Published: December 2022

Adequate vitamin D status is essential for bone health. New randomized controlled trials investigating the effect of vitamin D supplementation on bone health have recently been published. This position statement updates and expands on the previous 2015 position statement of the Korean Society for Bone and Mineral Research on the adequate vitamin D status for healthy older adults (age ≥ 70 years) and those at high risk of osteoporosis and fracture (adults on osteoporosis medications) to maintain serum 25-hydroxy-vitamin D (25[OH]D) levels ≥ 20 ng/mL but < 50 ng/mL. A serum 25(OH)D level of 30 ng/mL may be beneficial for those on anti-resorptives. Vitamin D can be obtained from ultraviolet light exposure and diet. To reach the target vitamin D status through intake, adults must consume at least 400 IU/day to reach 20 ng/mL and 800 to 1,000 IU/day to reach 30 ng/mL. Foods familiar to the Korean diet that are high in vitamin D content or consumed frequently enough to positively impact vitamin D status are introduced in addition to the amount required to help reach one’s target vitamin D status.
Daily Walking Accompanied with Intermittent Resistance Exercise Prevents Osteosarcopenia: A Large Cohort Study
Authors: Lee Sangyeob , Kim Ji-Seok , Park Ki-Soo , Baek Kyung-Wan , Yoo Jun-Il
Published: December 2022

Background: This study aimed to analyze the effects of walking and resistance exercises on bone structure, bone mineral density (BMD), and skeletal muscle mass. We used data from the fourth Korean National Health and Nutrition Examination Survey (KNHANES).Methods: A total of 3,477 participants aged ≥19 years underwent hip structural analysis (HSA), BMD, and skeletal muscle index (SMI). All radiologic evaluations were performed using dual energy X-ray absorptiometry (DXA). The Korean short version of the International Physical Activity Questionnaire was used to measure physical activity status. The physical activity recommendations of the American College of Rheumatology Work Group Panel were used to evaluate the extent of activity.Results: The BMD and SMI in the group in which walking activity was performed 5 days or more per week for at least 30 min per day were significantly higher than those in the group in which walking activity was not performed. HSA and SMI in the group in which resistance exercise was performed 2 days or more per week for at least 30 min per day were found to be significantly higher than those in the group in which strengthening exercises were not performed.Conclusions: If resistance exercise and walking are combined, bone loss and muscle loss are prevented maintaining cortical thickness in the elderly. Walking for more than 5 days a week and resistance exercise for more than 2 days a week will help to maintain the skeletal muscle as well as the cortex around the femur neck, thus helping to prevent fragility fractures in older individuals.
The mechanics underpinning non-deterministic computation in cortical neural networks
Authors: Stoll Elizabeth A
Published: December 2022

Cortical neurons allow random electrical noise to contribute to the likelihood of firing a signal. Previous approaches have involved statistically modeling signaling outcomes in neuronal populations, or modeling the dynamical relationship between membrane potential, ion channel activation, and ion conductance in individual neurons. However, these methods do not mechanistically account for the role of random electrical noise in gating the action potential. Here, the membrane potential of a cortical neuron is modeled as the uncertainty in all component pure states, or the amount of information encoded by that computational unit. With this approach, each neuron computes the probability of transitioning from an off-state to an on-state, with the macrostate of each computational unit being a function of all component microstates. Component pure states are integrated into a physical quantity of information, and the derivative of this high-dimensional probability density yields eigenvalues, or an internally-consistent observable system state at a defined point in time. In accordance with the Hellman-Feynman theorem, the resolution of the system state is paired with a spontaneous shift in charge distribution, and so this defined system state instantly becomes the past as a new probability density emerges. This model of Hamiltonian mechanics produces testable predictions regarding the wavelength of free energy released upon information compression. Overall, this model demonstrates how cortical neurons might achieve non-deterministic signaling outcomes through noisy coincidence detection.
rcCAE: a convolutional autoencoder method for detecting intra-tumor heterogeneity and single-cell copy number alterations
Authors: Yu Zhenhua , Liu Furui , Shi Fangyuan , Du Fang
Published: December 2022

Intra-tumor heterogeneity (ITH) is one of the major confounding factors that result in cancer relapse, and deciphering ITH is essential for personalized therapy. Single-cell DNA sequencing (scDNA-seq) now enables profiling of single-cell copy number alterations (CNAs) and thus aids in high-resolution inference of ITH. Here, we introduce an integrated framework called rcCAE, to accurately infer cell subpopulations and single-cell CNAs from scDNA-seq data. A convolutional autoencoder (CAE) is employed in rcCAE to learn latent representation of the cells as well as distill copy number information from noisy read counts data. This unsupervised representation learning via the CAE model makes it convenient to accurately cluster cells over the low-dimensional latent space, and detect single-cell CNAs from enhanced read counts data. Extensive performance evaluations on simulated datasets show rcCAE outperforms existing CNA calling methods, and is highly effective in inferring clonal architecture. Furthermore, evaluations of rcCAE on two real datasets demonstrate it is able to provide more refined clonal structure, of which some details are lost in clonal inference based on integer copy numbers.
NetGO 3.0: Protein Language Model Improves Large-scale Functional Annotations
Authors: Wang Shaojun , You Ronghui , Liu Yunjia , Xiong Yi , Zhu Shanfeng
Published: December 2022

As one of the state-of-the-art automated function prediction (AFP) methods, NetGO 2.0 integrates multi-source information to improve the performance. However, it mainly utilizes the proteins with experimentally supported functional annotations without leveraging valuable information from a vast number of unannotated proteins. Recently, protein language models have been proposed to learn informative representations (e.g., Evolutionary Scale Modelling (ESM)-1b embedding) from protein sequences based on self-supervision. We represent each protein by ESM-1b and use logistic regression (LR) to train a new model, LR-ESM, for AFP. The experimental results show that LR-ESM achieves comparable performance with the best-performing component of NetGO 2.0. Therefore, by incorporating LR-ESM into NetGO 2.0, we develop NetGO 3.0 to improve the performance of AFP extensively. NetGO 3.0 is freely accessible athttps://dmiip.sjtu.edu.cn/ng3.0.
ERBB-activated myofibroblastic cancer-associated fibroblasts promote local metastasis of pancreatic cancer
Authors: Mucciolo Gianluca , Henríquez Joaquín Araos , Teles Sara Pinto , Manansala Judhell S. , Jihad Muntadher , Li Wenlong , Lloyd Eloise G. , Cheng Priscilla S.W. , Biffi Giulia
Published: December 2022

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Cancer-associated fibroblasts (CAFs) are recognized potential therapeutic targets, but poor understanding of these heterogeneous cell populations has limited the development of effective treatment strategies. We previously identified TGF-β as a main driver of myofibroblastic CAFs (myCAFs). Here, we show that EGFR/ERBB2 signaling is induced by TGF-β in myCAFs through an autocrine process mediated by the ERBB ligand amphiregulin. Inhibition of this ERBB-signaling network in PDAC organoid-derived cultures and mouse models impacts distinct CAF subtypes, providing insights into mechanisms underpinning their heterogeneity. Remarkably, ERBB-activated myCAFs promote local PDAC metastasis in mice, unmasking functional significance in myCAF heterogeneity. Finally, analyses of other cancer datasets suggest these processes might operate in other malignancies. These data provide functional relevance to CAF heterogeneity and identify a potential target for preventing local tumor invasion in PDAC.