bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of HcaA, a novel autotransporter protein in
Helicobacter cinaedi
, and its role in host cell adhesion
Authors: Aoki Sae , Mori Shigetarou , Matsui Hidenori , Shibayama Keigo , Kenri Tsuyoshi , Rimbara Emiko
Published: November 2023

Helicobacter cinaedi
infects the human gut and causes invasive infections such as bacteremia and cellulitis through bacterial translocation. However, the mechanism by which
H. cinaedi
attaches to host cells and establishes infection remains unclear. This study aimed to investigate the relationship between a novel putative autotransporter protein,
H. cinaedi
autotransporter protein A (HcaA), and its role in pathogenicity. The cytotoxicity of
H. cinaedi
infection in colon epithelial cell lines (Caco-2 and HT29) was assessed using a lactate dehydrogenase assay, and it was found that cytotoxicity significantly decreased upon HcaA knockout. Adhesion assays further revealed that the HcaA-knockout strain showed significantly reduced attachment to the human epithelial colorectal adenocarcinoma (Caco-2) cell line compared to that of the wild-type strain. Moreover, the recombinant HcaA protein demonstrated strong adhesion properties to the human monocytic cell line (U937). The adhesive activity was diminished when the Arg-Gly-Asp (RGD) motif in HcaA was replaced with RAD, indicating that the RGD motif in HcaA is crucial for host cell adhesion. To determine the role of HcaA in
H. cinaedi
infection
in vivo
, C57BL/6 mice were orally infected with wild-type and HcaA-knockout
H. cinaedi
strains. Bacterial colonization was assessed 7, 14, and 28 days post-infection. At 7 days post-infection, colonization was significantly lower in mice infected with the HcaA-knockout strain compared to those infected with the wild-type strain. In conclusion, our findings suggest that HcaA, a novel putative autotransporter protein in
H. cinaedi
, plays a significant role as an adhesin in establishing colonization.

IMPORTANCE

Helicobacter
species are classified as gastric or enterohepatic according to their habitat. Among enterohepatic
Helicobacter
species, which inhabit the intestine, colon, and liver,
Helicobacter cinaedi
has been most frequently isolated from humans.
H. cinaedi
often causes bacteremia and cellulitis in immunocompromised hosts. Here, we focused on the
H. cinaedi
autotransporter protein A (HcaA), a novel virulence factor in
H. cinaedi
. We discovered that HcaA contributes to cell adhesion via its Arg-Gly-Asp motif. Furthermore, in animal experiments, bacterial colonization was reduced in mice infected with HcaA-knockout strains, supporting the hypothesis that HcaA contributes to
H. cinaedi
adhesion to host cells. Our study provides a novel mechanism for the establishment of
H. cinaedi
infections and provides new insights into the role of autotransporter proteins in the establishment of
Helicobacter
infection.
Development of a murine model to study the cerebral pathogenesis of
Aspergillus fumigatus
Authors: Kelty Martin T. , Beattie Sarah R.
Published: November 2023

Fungal infections of the central nervous system are associated with high mortality and limited treatment options due to the poor permeability of the blood brain barrier to most antifungal drugs. The most common pathogenic mold is
Aspergillus fumigatus
, which typically causes invasive pulmonary disease that can disseminate to extrapulmonary organs, including the brain, resulting in cerebral aspergillosis (CA). Currently, the best treatment option for CA is antifungal therapy combined with resection of infected tissue; however, mortality rates of these infections still approach 100%. Despite these unacceptably high mortality rates, relatively little is known about the fungal determinants that allow
Aspergillus
to successfully establish infection and grow within the brain. Here, we present a murine model designed to study the fungal pathogenesis of CA using tail vein inoculation in C5-complement-deficient mice. In this model, mice develop a robust fungal burden in the brain and display hallmarks of invasive aspergillosis seen in both murine models of invasive aspergillosis and in human cases of CA. We highlight the role of one fungal transcription factor, PacC, in the hematogenous dissemination of
A. fumigatus
to extrapulmonary organs including the brain. This model will enable pathogenesis studies in a largely unexplored area of
A. fumigatus
infections with the goal of identifying novel targets and pathways for the development of more efficacious antifungal therapies to treat these infections.

IMPORTANCE

Molds are environmental fungi that can cause disease in immunocompromised individuals. The most common pathogenic mold is
Aspergillus fumigatus,
which is typically inhaled into the lungs and causes invasive pulmonary disease. In a subset of these patients, this infection can spread from the lungs to other organs including the brain, resulting in cerebral aspergillosis. How
A. fumigatus
causes brain disease is not well understood and these infections are associated with extremely high mortality rates. Thus, we developed an animal model to study the pathogenesis of cerebral aspergillosis to better understand this disease and develop better treatments for these life-threatening infections.
Multiple phosphorylation sites regulate the activity of the repressor Mig1 in
Candida albicans
Authors: Ramírez-Zavala Bernardo , Betsova Darina , Schwanfelder Sonja , Krüger Ines , Mottola Austin , Krüger Thomas , Kniemeyer Olaf , Brakhage Axel A. , Morschhäuser Joachim
Published: November 2023

The highly conserved heterotrimeric protein kinase SNF1 is important for metabolic adaptations in the pathogenic yeast
Candida albicans
. A key function of SNF1 is to inactivate the repressor protein Mig1 and thereby allow the expression of genes that are required for the utilization of alternative carbon sources when the preferred carbon source, glucose, is absent or becomes limiting. However, how SNF1 controls Mig1 activity in
C. albicans
has remained elusive. Using a phosphoproteomics approach, we found that Mig1 is phosphorylated at multiple serine residues. Replacement of these serine residues by nonphosphorylatable alanine residues strongly increased the repressor activity of Mig1 in cells lacking a functional SNF1 complex, indicating that additional protein kinases are involved in the regulation of Mig1. Unlike wild-type Mig1, whose levels strongly decreased when the cells were grown on sucrose or glycerol instead of glucose, the levels of a mutant Mig1 protein lacking nine phosphorylation sites remained high under these conditions. Despite the increased protein levels and the absence of multiple phosphorylation sites, cells with a functional SNF1 complex could still sufficiently inhibit the hyperactive Mig1 to enable wild-type growth on alternative carbon sources. In line with this, phosphorylated forms of the mutant Mig1 were still detected in the presence and absence of a functional SNF1, demonstrating that Mig1 contains additional, unidentified phosphorylation sites and that downstream protein kinases are involved in the control of Mig1 activity by SNF1.

IMPORTANCE

The SNF1 protein kinase signaling pathway, which is highly conserved in eukaryotic cells, is important for metabolic adaptations in the pathogenic yeast
Candida albicans
. However, so far, it has remained elusive how SNF1 controls the activity of one of its main effectors, the repressor protein Mig1 that inhibits the expression of genes required for the utilization of alternative carbon sources when glucose is available. In this study, we have identified multiple phosphorylation sites in Mig1 that contribute to its inactivation. Mutation of these sites strongly increased Mig1 repressor activity in the absence of SNF1, but SNF1 could still sufficiently inhibit the hyperactive Mig1 to enable growth on alternative carbon sources. These findings reveal features of Mig1 that are important for controlling its repressor activity. Furthermore, they demonstrate that both SNF1 and additional protein kinases regulate Mig1 in this pathogenic yeast.
Differences in risk and costs between prehospital identified low-risk men and women with chest pain
Authors: Aarts Goaris W A , Camaro Cyril , Rodwell Laura , Adang Eddy M M , van Hout Roger , Brok Gijs , Hoare Anouk , de Pooter Frank P C , de Wit Walter , Cramer Gilbert E , van Kimmenade Roland R J , Ouwendijk Eva , Rutten Martijn , Zegers Erwin , van Geuns Robert-Jan M , Gomes Marc E R , Damman Peter , van Royen Niels
Published: November 2023

Objective

Prehospital rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in low-risk patient with a point-of-care troponin measurement reduces healthcare costs with similar safety to standard transfer to the hospital. Risk stratification is performed identical for men and women, despite important differences in clinical presentation, risk factors and age between men and women with NSTE-ACS. Our aim was to compare safety and healthcare costs between men and women in prehospital identified low-risk patients with suspected NSTE-ACS.

Methods

In the Acute Rule-out of non-ST-segment elevation acute coronary syndrome in the (pre)hospital setting by HEART (History, ECG, Age, Risk factors and Troponin) score assessment and a single poInt of CAre troponin randomised trial, the HEAR (History, ECG, Age and Risk factors) score was assessed by ambulance paramedics in suspected NSTE-ACS patients. Low-risk patients (HEAR score ≤3) were included. In this substudy, men and women were compared. Primary endpoint was 30-day major adverse cardiac events (MACE), secondary endpoints were 30-day healthcare costs and the scores for the HEAR score components.

Results

A total of 863 patients were included, of which 495 (57.4%) were women. Follow-up was completed in all patients. In the total population, MACE occurred in 6.8% of the men and 1.6% of the women (risk ratio (RR) 4.2 (95% CI 1.9 to 9.2, p<0.001)). In patients with ruled-out ACS (97% of the total population), MACE occurred in 1.4% of the men and in 0.2% of the women (RR 7.0 (95% CI 2.0 to 14.2, p<0.001). Mean healthcare costs were €504.55 (95% CI €242.22 to €766.87, p<0.001) higher in men, mainly related to MACE.

Conclusions

In a prehospital population of low-risk suspected NSTE-ACS patients, 30-day incidence of MACE and MACE-related healthcare costs were significantly higher in men than in women.

Trial registration number

NCT05466591.
Twelve-month follow-up effects of cognitive training after heart valve surgery on cognitive functions and health-related quality of life: a randomised clinical trial
Authors: Butz Marius , Gerriets Tibo , Sammer Gebhard , El-Shazly Jasmin , Tschernatsch Marlene , Braun Tobias , Meyer Rolf , Schramm Patrick , Doeppner Thorsten R , Böning Andreas , Mengden Thomas , Choi Yeong-Hoon , Schönburg Markus , Juenemann Martin
Published: November 2023

Objectives

Postoperative cognitive decline (POCD) or decreased health-related quality of life (HQL) have been reported after cardiac surgery. A previous investigation showed beneficial effects of postoperative cognitive training on POCD and HQL 3 months after heart surgery. Here, we present the 12-month follow-up results.

Methods

This bicentric, 1:1 randomised and treatment-as-usual controlled trial included elderly patients scheduled for elective heart valve surgery. The training consisted of paper-and-pencil-based exercises practising multiple cognitive functions for 36 min/day 6 days/week over a period of 3 weeks. Neuropsychological tests and questionnaires assessing HQL (36-Item Short Form Health Survey (SF-36)) and cognitive failures in daily living (Cognitive Failures Questionnaire) were performed presurgery and 12 months after training.

Results

Twelve months post training, the training group (n=30) showed improvements in HQL compared with the control group (n=28), especially in role limitations due to physical health (U=−2.447, p=0.015, η2=0.109), role limitations due to emotional problems (U=−2.245, p=0.025, η2=0.092), pain (U=−1.979, p=0.049, η2=0.068), average of all SF-36 factors (U=−3.237, p<0.001, η2=0.181), health change from the past year to the present time (U=−2.091, p=0.037, η2=0.075), physical component summary (U=−2.803, p=0.005, η2=0.138), and mental component summary (U=−2.350, p=0.018, η2=0.095). Furthermore, the training group (n=19) showed an improvement compared with the control group (n=27) in visual recognition memory (U=−2.137, p=0.034, η2=0.099). POCD frequency was 22% (n=6) in the control group and 11% (n=2) in the training group (χ²(1) =1.06, p=0.440; OR=2.43, 95% CI 0.43 to 13.61).

Conclusion

In conclusion, postoperative cognitive training shows enhancing effects on HQL in cardiac surgery patients after 12 months.
Superiority of left heart deformation in early anthracycline-related cardiac dysfunction detection
Authors: Giang M Nhat , Nguyen H Hai , Vo Duc Tan , Ho Huynh Quang Tri , Phan Duc Thi Hong , Chau Ngoc-Hoa
Published: November 2023

Objective

This study aimed to assess the incidence of early cancer therapy-related cardiac dysfunction (CTRCD) and the characteristics of left and right heart deformations during anthracycline chemotherapy.

Methods

We prospectively enrolled a cohort of 351 chemotherapy-naïve women with breast cancer and cardiovascular risk factors who were scheduled to receive anthracycline. The left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LV-GLS) and right ventricular and left atrial longitudinal strains were evaluated using echocardiography at baseline, before every subsequent cycles and at 3 weeks after the final anthracycline dose. CTRCD was defined as a new LVEF reduction by ≥10 percentage points to an LVEF<50% and/or a new relative decline in GLS by >15% from the baseline value.

Results

Eighteen (5.1%) patients had evidence of asymptomatic CTRCD during anthracycline treatment, and 50% developed CTRCD before completing the chemotherapy regimen. In the CTRCD group, while LV-GLS decrease significantly after the first dose of anthracycline, the reduction of right ventricular free-wall longitudinal strain and left atrial reservoir strain were observed after the second dose. Other strain indices could not be used to identify early CTRCD.

Conclusions

Cardiotoxicity appeared soon after the initiation of anthracycline chemotherapy. Among the left-heart and right-heart mechanics, LV-GLS remains the best deformation indicator for detecting early CTRCD.
Mechanism for conversion between twist and writhe of DNA based on chiral gauge potential
Authors: Yang Huimin , Shi Xuguang
Published: November 2023

It is well known that the linking number is the sum of the writhing number and twisting number based on white’s formula. In this work, we reveal the underlying physics of the transformation between the twist and the writhe of deoxyribonucleic acid (DNA). In the framework of the Landau model, we describe the local interaction between the base pairs by using the chiral gauge potential. With the chiral gauge potential, we develop a geometrical model where the free energy density is given by the geometrical parameters, including the normal curvature, the geodesic curvature, and the geodesic torsion. It is shown that the chiral gauge potential plays a crucial role in the conversion between the twist and the writhe of DNA. By using the invariance of the self-linking number, we find that when the total twisting number is changed by −Δ Q, the writhing number is changed by Δ Q. Our findings not only deepen the understanding of the topological nature of DNA, but also provide a physical model for the research of the conformation of DNA.
A Study on Corrosion of Al-Clad Coin Cell Cases in High-Voltage Li-Ion Battery
Authors: Zhang Sheng S.
Published: November 2023

Aluminum-coated (Al-Clad) coin cell case has long been introduced to evaluate high-voltage cathode materials and electrolytes in battery research. However, our study on graphite/LiNi0.80Co0.10Mn0.10O2 (Gr/NCM811) coin cells indicates that the Al-Clad case resulted in even worse performance than the pristine stainless steel (SS) case. Post-mortem observation finds that the Al-Clad case was severely corroded, while the SS case seems to remain intact. To understand this unusual phenomenon, the corrosion behavior of the Al-Clad cases in LiPF6 electrolyte and lithium bis(fluorosulfonyl)imide (LiFSI) electrolyte, respectively, is studied. It is shown that the coating of Al on the Al-Clad cases is not dense, allowing liquid electrolytes to permeate through and contact the underlying SS core case, forming galvanic cells between the Al coating and the SS core case. At high potentials, the galvanic cells reduce the over-potential of Al oxidation, promoting corrosion of the Al coating. As such, the Al coating does not protect the underlying SS core case, oppositely, making the corrosion of itself more severe. The results of this work reveal that to support high-voltage applications, the coating of Al on the Al-Clad cases must be dense, otherwise, it makes the corrosion worse.
Determining the Turn-On Voltage of GaN-Based Light-Emitting Diodes: From Near-Ultraviolet to Green Spectra
Authors: Islam Abu Bashar Mohammad Hamidul , Shin Dong-Soo , Kwak Joon Seop , Shim Jong-In
Published: November 2023

This work investigates the turn-on voltage (V
on) estimation methods from experimental data of InGaN-based multiple-quantum-well light-emitting diodes (LEDs) with emission spectra from near-ultraviolet to green wavelengths. Three different methods are examined: fixed current intercept, linear fitting of current-voltage curve, and the minimum ideality factor (n
ideal). The voltage at minimum n
ideal consistently represents the on-state of LEDs since it describes the carrier recombination processes reflected in light output power (LOP) and the external quantum efficiency (EQE). Beyond the voltage at minimum n
ideal, samples’ LOPs start to increase abruptly, with the EQEs reaching ≥ 54% of the peak EQE values. For V
on determined by other methods, samples’LOPs are already turned on and the EQEs exceed their peak value. Therefore, using the minimum n
ideal is a suitable method for determining Von of an LED.
Cardioprotective antihyperglycemic drugs ameliorate endoplasmic reticulum stress
Authors: Mooradian Arshag D. , Haas Michael J.
Published: November 2023

Cellular stress, notably oxidative, inflammatory, and endoplasmic reticulum (ER) stress, is implicated in the pathogenesis of cardiovascular disease. Modifiable risk factors for cardiovascular disease such as diabetes, hypercholesterolemia, saturated fat consumption, hypertension, and cigarette smoking cause ER stress whereas currently known cardioprotective drugs with diverse pharmacodynamics share a common pleiotropic effect of reducing ER stress. Selective targeting of oxidative stress with known antioxidative vitamins has been ineffective in reducing cardiovascular risk. This “antioxidant paradox” is partially attributed to the unexpected aggravation of ER stress by the antioxidative agents used. In contrast, some of the contemporary antihyperglycemic drugs inhibit both oxidative stress and ER stress in human coronary artery endothelial cells. Unlike sulfonylureas, meglitinides, α glucosidase inhibitors, and thiazolidinediones, metformin, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors are the only antihyperglycemic drugs that reduce ER stress caused by pharmacological agents (tunicamycin) or hyperglycemic conditions. Clinical trials with selective ER stress modifiers are needed to test the suitability of ER stress as a therapeutic target for cardiovascular disease.
Prevalence of Gastrointestinal Parasites in Pigs: A Preliminary Study in Tolon and Kumbungu Districts, Ghana
Authors: Addy Francis , Adu-Bonsu Gideon , Akurigo Comfort A. , Abukari Iddrisu , Suleman Hamidatu , Quaye Lydia
Published: November 2023

Pigs are important livestock that contribute to the economy and food security of Ghana, but the productivity of the sector is hindered by factors such as parasitic disease infections. Here, we detected the prevalence and polyparasitism of gastrointestinal parasites in pigs from selected farms in the Tolon and Kumbungu districts. Faeces of the animals were screened for parasite eggs using the sedimentation and flotation methods. From 56 pigs screened, 91.1% (

CI
=
95

%;

χ

2

=
0.212

) of them had parasitic infections, and affected pigs harboured 1–5 distinct parasites with the most occurring being Strongyloides ransomi (46.43%). Other parasites identified included Hyostrongylusrubidus, Ascaris suum, Trichuris suis, Physocephalus sexalatus, and Coccidia, among others. Parasitism was more frequent in pigs under 2 years (94%) than older ones (66.67%). The high prevalence of GI parasites was attributed to poor husbandry practices and inadequate of veterinary care for the animals. The situation can be improved by farmer education on good husbandry practices and regular deworming of pigs.
Antimicrobial-Resistant Environmental Bacteria Isolated Using a Network of Honey Bee Colonies (Apis mellifera L. 1758)
Authors: Cilia Giovanni , Resci Ilaria , Scarpellini Raffaele , Zavatta Laura , Albertazzi Sergio , Bortolotti Laura , Nanetti Antonio , Piva Silvia
Published: November 2023

The phenomenon of antibiotic resistance stands as a paramount health challenge in the contemporary era. Within a One Health approach, it becomes crucial to effectively track the dissemination of antibiotic resistance, not only within humans and animals but also within the environment. To investigate the environment, the honey bee (Apis mellifera) has emerged as a prominent environmental bioindicator due to its social, behavioral, and morphological features. The objective of this study was to describe the antimicrobial resistance (AMR) patterns of bacterial isolates from the body surface and the gut of honey bees sampled from 33 colonies throughout the Emilia-Romagna region (Italy). A total of 608 strains were examined for 19 distinct antimicrobial compounds from various classes, and the results showed that more than 50% of the isolates for eight out of nine provinces showed characteristics of nonsusceptibility toward amoxicillin and penicillin, and, generally, 98.19% of isolated strains were considered AMR and 74.67% exhibited multidrug resistance (MDR) characteristics, more frequent in Gram-negative strains (87.74%) than in Gram-positive ones (60.34%). Additionally, a significant correlation with a lower prevalence of MDR bacteria was demonstrated for one province (Ferrara, odds ratio (OR) = 3.33, (1.67; 6.64),

p
=
0.0006

). In conclusion, this study provides evidence for the utility of A. mellifera colonies as bioindicators for MDR bacteria, enabling their characterization and distribution at a geographical level. Additional investigations are required to further explore the potential role of honey bees as bioindicators for antimicrobial-resistant bacteria, particularly in terms of their association with environmental characteristics.
Determinants and Characteristics of Insulin Dose Requirements in Children and Adolescents with New-Onset Type 1 Diabetes: Insights from the INSENODIAB Study
Authors: Beckers Maude , Polle Olivier , Gallo Paola , Bernard Noémie , Bugli Céline , Lysy Philippe A.
Published: November 2023

Aims. New-onset type 1 diabetes mellitus (T1D) in pediatric patients represents a clinical challenge for initial total daily insulin dosing (TIDD) due to substantial heterogeneity in practice and lack of consensus on the optimal starting dose. Our INSENODIAB (INsulin SEnsitivity in New Onset type 1 DIABetes) study is aimed at (1) exploring the influence of patient-specific characteristics on insulin requirements in pediatric patients with new-onset T1D; (2) constructing a predictive model for the recommended TIDD tailored to individual patient profiles; and (3) assessing potential associations between TIDD and patient outcomes at follow-up intervals of 3 and 12 months. Methods. We conducted a comprehensive analysis of medical records for children aged 6 months to 18 years, hospitalized for new-onset T1D from 2013 to 2022. The study initially involved multivariable regression analysis on a retrospective cohort (rINSENODIAB), incorporating baseline variables. Subsequently, we validated the model robustness on a prospective cohort (pINSENODIAB) with a significance threshold of 5%. The model accuracy was assessed by Pearson’s correlation. Results. Our study encompassed 103 patients in the retrospective cohort and 80 in the prospective cohort, with median TIDD at diagnosis of 1.1 IU/kg BW/day (IQR 0.5). The predictive model for optimal TIDD was established using baseline characteristics, resulting in the following formula:

TIDD
 

IU
/
d

=

0.09
×
Age
2

+

0.68
×
%
Weight
 
Loss

+

28.60
×
Veinous
 
pH

−

1.03
×
Veinous
 
bicarbonates

+

0.81
×
Weight

−
194.63

. Validation of the model using the pINSENODIAB cohort demonstrated a significant Pearson correlation coefficient of 0.74. Notably, no significant correlation was observed between TIDD at diagnosis and partial remission markers (IDAA1C, C-peptide) at 3- and 12-months postdiagnosis time points. Conclusions. In the context of new-onset T1D in pediatric patients, we identified key influencing factors for determining optimal TIDD, including age, percentage of weight loss, weight, veinous pH, and bicarbonates. These findings have paved the way for the development of a dosing algorithm to potentially expedite glycemic control stabilization and facilitate a more individualized approach to treatment regimens.
Flow Dynamics of Eyring–Powell Nanofluid on Porous Stretching Cylinder under Magnetic Field and Viscous Dissipation Effects
Authors: Rikitu Ebba Hindebu
Published: November 2023

The current paper scrutinized the flow dynamics of Eyring–Powell nanofluid on porous stretching cylinder under the effects of magnetic field and viscous dissipation by employing Cattaneo–Christov theory. In order to study impacts of thermophoretic force and Brownian motion, the two-phase (Buongiorno) model is considered. As a consequence, very nonlinear PDEs that govern flow problem were formulated, transformed into ODEs via relevant similarity variables, as well as tackled by utilizing R-K-45 integration scheme along with the shooting technique in the MATLAB R2018a software. Consequently, the numerical simulations reveal that Eyring–Powell fluid, curvature, velocity ratio parameters have the propensity to raise nanofluid velocity. Nanofluid temperature shows an increasing pattern with magnetic, curvature, dissipative heating, and thermophoresis parameters. Besides, Prandtl number, Eyring–Powell fluid, velocity ratio, thermal relaxation time, and porous parameters indicate the declining impact against the nanofluid temperature. Hence, the porous medium reasonably and successfully managed nanofluid temperature as well as the overall thermal system in terms of system cooling. The concentration profile gets fall down with escalating values of Schmidt number, magnetic, curvature, dissipative heating, thermophoresis, Brownian motion, and solutal relaxation time parameters. Moreover, coefficient of the skin friction gets rise for larger values of Eyring–Powell fluid, magnetic and curvature parameters however porous medium and velocity ratio parameters reveal the opposite trends on it. The magnetic, curvature, Eyring–Powell fluid, velocity ratio, and dissipative heating parameters indicate increasing impacts on both Nusselt

N
u

and Sherwood

S
h

numbers even though both

N
u

and

S
h

get cut down with the porous medium parameter. Moreover, an excellent and sound agreement was attained up on comparing coefficients of the skin friction for the current result against that of previously published literatures under some limiting cases.
FDA Approval Summary: Ivosidenib in Combination with Azacitidine for Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia with an IDH1 Mutation
Authors: Woods Ashley , Norsworthy Kelly J. , Wang Xin , Vallejo Jonathon , Chiu Yuen Chow Edwin , Li Ruo-Jing , Sun Jielin , Charlab Rosane , Jiang Xiling , Pazdur Richard , Theoret Marc R. , de Claro R. Angelo
Published: November 2023

On May 25, 2022, FDA approved a supplemental application for ivosidenib (Tibsovo; Servier) extending the indication in patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML) in older adults or those with comorbidities to include the combination with azacitidine. The efficacy of ivosidenib in combination with azacitidine was evaluated in Study AG120-C-009, a phase 3, multicenter, double-blind, randomized (1:1), controlled study of ivosidenib or matched placebo in combination with azacitidine in adults with previously untreated AML with an IDH1 mutation who were 75 years or older or had comorbidities that precluded use of intensive induction chemotherapy. Efficacy was established on the basis of improved event-free survival and overall survival on the ivosidenib + azacitidine arm [HR, 0.35; 95% confidence interval (CI), 0.17–0.72; P = 0.0038, and HR, 0.44; 95% CI, 0.27–0.73; P = 0.0010], respectively. Furthermore, the rate and duration of complete remission (CR) were improved with ivosidenib versus placebo [CR 47% versus 15%, two-sided P < 0.0001; median duration of CR not estimable (NE; 95% CI, 13.0–NE) months versus 11.2 (95% CI, 3.2–NE) months. The safety profile of ivosidenib in combination with azacitidine was consistent with that of ivosidenib monotherapy, with important adverse reactions including differentiation syndrome (15%) and QT interval prolongation (20%).
Clinical Features, Diagnosis, and Treatment of Congenital and Neonatal Tuberculosis: A Retrospective Study
Authors: Zhou Yujiao , Zhu Kun , Zhang Xiayi , Zhu Zheyi , Jiang Li , Xing Linlin , Xu Binyue , Ai TingTing , Liu Quanbo , Zhao Ruiqiu , Xu Ximing , Chen Juan , Zhang Zhenzhen
Published: November 2023

Introduction: Limited studies have explored the clinical features, treatment, and prognosis of neonatal tuberculosis (TB). Here, we attempted to delineate the clinical characteristics of neonatal TB, which may help clinicians further understand this disease. Methods: A retrospective analysis of neonates diagnosed with congenital and/or neonatal TB disease from January 2010 to December 2020 was performed. Information on the demographic and epidemiological features, clinical symptoms, laboratory and imaging examinations, therapeutic regimens, and outcomes was collected. Kaplan-Meier analysis was used to present the time to disease onset, time to diagnosis, etc. Results: Forty-eight cases of neonatal TB were classified into congenital (n = 33) and postnatal (n = 15). The median time to disease onset in postnatal group was significantly longer than that in congenital group. Positive results for gastric fluid acid-fast bacilli, TB culture, Xpert MTB/RIF, interferon-γ release assay (IGRA), and tuberculin skin test were detected in 26/48 (54.2%), 14/34 (41.2%), 11/18 (61.1%), 19/29 (65.5%), and 8/24 (33.3%) patients, respectively. For lymphadenopathy, computed tomography (CT) scans showed a higher detection rate than did X-ray (80.0% vs. 0). Of the 48 infants, 44/48 (91.7%) received anti-TB therapy, and 33/44 (75%) were clinically improved or cured after 22.1 months (interquartile range: 12.4–27.7) of follow-up. Drug-induced liver injury occurred in 14/44 (31.8%) patients. Discussion/Conclusion: IGRA and Xpert MTB/RIF showed good positive rate in neonatal TB infection/disease. In cases where TB is presumed but etiological evidence is lacking, low-dose CT could be considered. Prompt treatment under careful surveillance is important for preventing mortality and avoiding severe adverse effects.
Machine Learning Facial Emotion Classifiers in Psychotherapy Research: A Proof-of-Concept Study
Authors: Steppan Martin , Zimmermann Ronan , Fürer Lukas , Southward Matthew , Koenig Julian , Kaess Michael , Kleinbub Johann Roland , Roth Volker , Schmeck Klaus
Published: November 2023

Background: New advances in the field of machine learning make it possible to track facial emotional expression with high resolution, including micro-expressions. These advances have promising applications for psychotherapy research, since manual coding (e.g., the Facial Action Coding System), is time-consuming. Purpose: We tested whether this technology can reliably identify in-session emotional expression in a naturalistic treatment setting, and how these measures relate to the outcome of psychotherapy. Method: We applied a machine learning emotion classifier to video material from 389 psychotherapy sessions of 23 patients with borderline personality pathology. We validated the findings with human ratings according to the Clients Emotional Arousal Scale (CEAS) and explored associations with treatment outcomes. Results: Overall, machine learning ratings showed significant agreement with human ratings. Machine learning emotion classifiers, particularly the display of positive emotions (smiling and happiness), showed medium effect size on median-split treatment outcome (d = 0.3) as well as continuous improvement (r = 0.49, p < 0.05). Patients who dropped out form psychotherapy, showed significantly more neutral expressions, and generally less social smiling, particularly at the beginning of psychotherapeutic sessions. Conclusions: Machine learning classifiers are a highly promising resource for research in psychotherapy. The results highlight differential associations of displayed positive and negative feelings with treatment outcomes. Machine learning emotion recognition may be used for the early identification of drop-out risks and clinically relevant interactions in psychotherapy.
Impairment of Autophagy Mediates the Uric-Acid-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells
Authors: Lu Yan , Zhang Hanlin , Han Min , Wang Ping , Meng Liping
Published: November 2023

Introduction: Hyperuricemia may be involved in the phenotypic transformation of vascular smooth muscle cells, thus promoting the occurrence of atherosclerosis, and autophagy may be one of the important links, but little is known about the specific molecular mechanism. Methods: We established a mouse model of hyperuricemia and studied the relationship between changes in autophagy levels and the phenotypic transformation of muscle cells. Results: Our study found that high uric acid levels promote the phenotypic transformation of muscle cells by inhibiting autophagy, thus enhancing their proliferation and migration abilities. If autophagy is restored, phenotypic transformation can be reversed by reducing the levels of the transcription factor Kruppel-like factor 4. Conclusion: Uric acid may induce the phenotypic transformation of muscle cells and promote the occurrence of atherosclerosis by disrupting normal autophagy.
Predictors of Recurrence and Progression in Poorly Differentiated Cutaneous Squamous Cell Carcinomas: Insights from a Real-Life Experience
Authors: Roccuzzo Gabriele , Orlando Giulia , Rumore Maria Rebecca , Morrone Antonio , Fruttero Enrico , Caliendo Virginia , Picciotto Franco , Sciarrillo Alberto , Quaglino Pietro , Cassoni Paola , Ribero Simone , Senetta Rebecca
Published: November 2023

Introduction: Surgery represents the primary treatment option for cutaneous squamous cell carcinoma (cSCC) aiming for complete tumor resection (R0). Recurrence and metastasis significantly affect survival and outcomes, and poorly differentiated (G3) cSCC is associated with a higher risk of recurrence. However, the specific clinical and histopathological features that predict recurrence and progression in G3-cSCC remain unclear. Methods: A retrospective analysis was conducted on a series of patients with primary G3-cSCC diagnosed at the Turin University Hospital between January 2016 and January 2021. After independent histological revision, logistic regression models were used to identify clinico-pathological predictors of cutaneous recurrence, lymphnode/metastatic progression, and both types of progression. Results: Among the 161 G3-cSCC patients, 80.1% (129/161) showed no signs of local recurrence or metastatic progression, while 19.9% (32 patients) had progressed. In the univariate logistic regression, tumor clinical diameter, depth of infiltration (DOI), and lymphovascular invasion (LVI) were identified as significant predictors across the various types of progression (p < 0.05). In the context of multivariate logistic regression, distinct models proved to be significant. For skin recurrence, a 3-variable model incorporating DOI (OR 1.16, 95% CI, 1.01–1.35, p = 0.050), LVI (OR 3.61, 95% CI, 1.11–11.8, p = 0.034), and desmoplasia (OR 3.45, 95% CI, 1.25–9.5, p = 0.017) was selected. Regarding lymphnode/metastatic progression, a 3-variable model combining pT2 (OR 6.10, 95% CI, 1.15–32.35, p = 0.034), pT3 (OR 14.33, 95% CI, 2.79–73.63, p = 0.001), and LVI (OR 3.86, 95% CI, 1.10–13.62, p = 0.036) was identified. Lastly, a 2-variable model for both types of progression consisted of vertical tumor thickness (OR 5.45, 95% CI, 1.11–27.32, p = 0.039) and LVI (OR 1.15, 95% CI, 1.04–1.26, p = 0.006). Conclusion: Tumor size, DOI, and LVI were significant predictors of recurrence and metastatic progression. Notably, the size of histologically defined tumor-free margins did not affect the risk of recurrence, whilst LVI emerged as a key predictor of all forms of progression. These findings provide insights into risk stratification and suggest that close monitoring and potential adjuvant therapies, such as radiation therapy, may be necessary especially for patients with lymphovascular involvement.
Clinical Studies on Topical Curcumin
Authors: Di Lorenzo Ritamaria , Forgione Federica , Bernardi Antonietta , Sacchi Antonia , Laneri Sonia , Greco Giovanni
Published: November 2023

Background: Curcumin is a polyphenolic compound present in turmeric (Curcuma longa). Curcumin, turmeric powder, and extracts are widely used in traditional Indian medicine and are active ingredients of dietary supplements and cosmeceutical products. The pharmacological properties of curcumin/turmeric as well as the studies performed in vitro, in animal models, and in volunteers have been the objects of a vast literature. Most of the clinical studies report on the effects of curcumin/turmeric administered orally, while only a few describe its topical applications. Summary: This review focuses on clinical studies in which curcumin/turmeric was applied topically to treat various skin conditions based on its antioxidant, anti-inflammatory, and antimicrobial properties. Key Messages: The clinical studies employing curcumin/turmeric as the only active ingredient allow us to appreciate its therapeutic potential without confounding contributions coming from additional pharmacologically active substances present in the same formulation. Curcumin/turmeric was regarded as an attractive alternative to conventional drugs, such as corticosteroids and antibiotics, thanks to its characteristics of a safe and well-tolerated natural substance.
Individualized Homeopathic Medicines in the Treatment of Post-COVID-19 Fatigue in Adults: Single-Blind, Randomized, Placebo-Controlled Trial
Authors: Saha Sangita , Singh Rakesh , Mani Ishika , Chakraborty Kalyan , Sarkar Paulami , Saha Subhranil , Rana Abhijit , Chattopadhyay Rajat
Published: November 2023

Introduction: The coronavirus disease 2019 (COVID-19) is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 fatigue is one of those challenges, becoming increasingly common as the pandemic evolves, as it impairs the quality of life of an individual. This trial attempts to identify the preliminary evidence of the efficacy of individualized homeopathic medicines (IHMs) against placebos in the treatment of post-COVID-19 fatigue in adults. Methods: A 3-month, single-blind, randomized, placebo-controlled, parallel-arm trial was conducted at the outpatient department of The Calcutta Homoeopathic Medical College and Hospital, India. Sixty participants were randomized in a 1:1 ratio to receive either IHMs (n = 30) or identical-looking placebos (n = 30). The primary and secondary outcome measures were the Fatigue Assessment Scale (FAS) and Outcome in Relation to Impact on Daily Living (ORIDL), respectively, measured every month, for up to 3 months. Comparative analysis was carried out on the intention-to-treat sample to detect group differences. Results: Group differences in both the primary (FAS total: F1, 58 = 14.356, p < 0.001) and secondary outcomes (ORIDL: F1, 58 = 210.986, p < 0.001) after 3 months favored IHMs against placebos. Lycopodium clavatum (11.7%), sulfur (11.7%), Arsenicum album (10%), and Thuja occidentalis (10%) were the most frequently indicated medicines. No harm, unintended effects, homeopathic aggravations, or any serious adverse events were reported from either of the groups. Conclusion: IHMs produced significantly better effects than placebos in the treatment of post-COVID-19 fatigue in adults. Definitive robust trials may be undertaken to confirm the findings.
Sympathetic-Immune Interactions during Different Types of Immune Challenge
Authors: del Rey Adriana , Besedovsky Hugo
Published: November 2023

Background: The neuro-endocrine regulation of immune functions is based on a complex network of interactions. As part of this series of articles, we refer here to immune-sympathetic interactions that are triggered by different types of immune challenge. Summary: We mention the initial hypothesis that led to the proposal that the sympathetic nervous system (SNS) is involved in immunoregulation. We next refer mainly to our initial work performed at a time when most immunologists were concentrated in clarifying aspects of the immune system that are essential for its regulation from within. The first approach was to explore whether immune responses to innocuous antigens and superantigens can elicit changes in the activity of the SNS, and their potential relevance for the regulation of the activity of the immune system. The following step was to explore whether comparable immune-SNS interactions are detected in different models of diseases with immune components, such as parasitic and viral infections and autoimmune pathologies. Key Messages: We pose some general considerations that may at least partially explain seemly discrepant findings, and remark the importance of interpreting immunoregulatory effects of the SNS together with other neuro-endocrine inputs that simultaneously occur when the activity of the immune system changes. Finally, we provide some arguments to re-consider the use of the expression “reflex” in immunology.
Early Identification of Patients with Potential Failure of Nonoperative Management for Gastroduodenal Peptic Ulcer Perforation
Authors: Kobayashi Toshimichi , Tabuchi Satoshi , Koganezawa Itsuki , Nakagawa Masashi , Yokozuka Kei , Ochiai Shigeto , Gunji Takahiro , Ozawa Yosuke , Sano Toru , Tomita Koichi , Chiba Naokazu , Hidaka Eiji , Kawachi Shigeyuki
Published: November 2023

Introduction: We aimed to identify objective factors associated with failure of nonoperative management (NOM) of gastroduodenal peptic ulcer perforation (GDUP) and establish a scoring model for early identification of patients in whom NOM of GDUP may fail. Methods: A total of 71 patients with GDUP were divided into NOM (cases of NOM success) and operation groups (cases requiring emergency operation or conversion from NOM to operation). Using logistic regression analysis, a scoring model was established based on the independent factors. The patients were stratified into low-risk and high-risk groups according to the scores. Results: Of the 71 patients, 18 and 53 were in the NOM and operation groups, respectively. Ascites in the pelvic cavity on computed tomography (CT) and sequential organ failure assessment (SOFA) score at admission were identified as independent factors for NOM failure. The scoring model was established based on the presence of ascites in the pelvic cavity on CT and SOFA score ≥2 at admission. The operation rates for GDUP were 28.6% and 86.0% in the low-risk (score, 0) and high-risk groups (scores, 2 and 4), respectively. Conclusion: Our scoring model may help determine NOM failure or success in patients with GDUP and make decisions regarding initial treatment.
Familial pulmonary fibrosis - a case report
Authors: Santos Mirelle Yumoto dos , Prada Vitória Raissa , Ghisi Caroline Uber
Published: November 2023

Introduction: Idiopathic pulmonary fibrosis (IPF), a chronic progressive idiopathic interstitial pneumonia (IIP), occasionally, IPF occurs in families. IPF is associated with an estimated survival of 20%–50% at 5 years. Familial pulmonary fibrosis (FPF) can be defined as the occurrence of at least two cases of some type or fibrous interstitial pneumonia in members of the same biological family. Is important to note that the forms of interstitial lung diseases that affect relatives not necessarily need to be the same. Adults with FPF are essentially indistinguishable from patientes with sporadic IPF in terms of clinical presentation, radiographic findings and histopathology, except that those with FPF tend to present it earlier.

Objective(s): To describe the clinical, functional, and radiological features of index cases of familial pulmonary fibrosis (FPF). Case overview: Male, 72 years old, seeks pulmonology service in October 16th, 2019 with cough, sputum and sinus pain. Denied dyspnea or other respiratory symptoms. Non-smoker, no alcoholism history, related physical activity 3 times per week and no environmental exposures. Treatment for sinusitis was indicated with return in 2 weeks. On return, he was asymptomatic. Unfortunately, he said that his 74-year old middle brother was hospitalized with severe dyspnea, mMRC 4, SpO2 91% using oxygen 4L in cateter and was diagnosed with non-specific interstitial pneumonia (NSIP). The CT scan revealed a tomographic pattern of NSIP, with a fibrous evolution form and emphysema. Also, he has a familiar history of an older brother who died 5 years ago, at the age of 80, with pulmonary fibrosis, and a CT scan usual intersticial pneumonia (UIP) pattern. The pulmonary auscultation had: a preserved vesicular murmur, mild bilateral “velcro-like” crackles in pulmonary basis, heard during middle to late inspiration, no wheezes. The patient didn’t accept to be submitted to invasive procedures, as bronchoscopy or surgical lung biopsy, because didn’t have respiratory symptoms (although the importance of these exams has been explained). The diagnosis of familial pulmonary fibrosis can be established when, despite having different tomographic patterns, siblings have in common the fibrous feature, as in this case. Even if the younger brother doesn’t have fibrosis yet, with the diagnosis confirmed by the other two brothers, the antifibrotic medication should be started.