bluuebunny/crossref_metadata_2025 huggingface dataset:
Orexin 2 receptor antagonism sex‐dependently improves sleep/wakefulness and cognitive performance in tau transgenic mice
Authors: Keenan Ryan J. , Daykin Heather , Metha Jeremy , Cornthwaite‐Duncan Linda , Wright David K. , Clarke Kyra , Oberrauch Sara , Brian Maddison , Stephenson Sarah , Nowell Cameron J. , Allocca Giancarlo , Barnham Kevin J. , Hoyer Daniel , Jacobson Laura H.
Published: August 2023

Background and Purpose

Tau pathology contributes to a bidirectional relationship between sleep disruption and neurodegenerative disease. Tau transgenic rTg4510 mice model tauopathy symptoms, including sleep/wake disturbances, which manifest as marked hyperarousal. This phenotype can be prevented by early transgene suppression; however, whether hyperarousal can be rescued after onset is unknown.

Experimental approach

Three 8‐week experiments were conducted with wild‐type and rTg4510 mice after age of onset of hyperarousal (4.5 months): (1) Tau transgene suppression with doxycycline (200 ppm); (2) inactive phase rapid eye movement (REM) sleep enhancement with the dual orexin receptor antagonist suvorexant (50 mg·kg−1·day−1); or (3) Active phase non‐NREM (NREM) and REM sleep enhancement using the selective orexin 2 (OX2) receptor antagonist MK‐1064 (40 mg·kg−1·day−1). Sleep was assessed using polysomnography, cognition using the Barnes maze, and tau pathology using immunoblotting and/or immunohistochemistry.

Key Results

Tau transgene suppression improved tauopathy and hippocampal‐dependent spatial memory, but did not modify hyperarousal. Pharmacological rescue of REM sleep deficits did not improve spatial memory or tau pathology. In contrast, normalising hyperarousal by increasing both NREM and REM sleep via OX2 receptor antagonism restored spatial memory, independently of tauopathy, but only in male rTg4510 mice. OX2 receptor antagonism induced only short‐lived hypnotic responses in female rTg4510 mice and did not improve spatial memory, indicating a tau‐ and sex‐dependent disruption of OX2 receptor signalling.

Conclusions and Implications

Pharmacologically reducing hyperarousal corrects tau‐induced sleep/wake and cognitive deficits. Tauopathy causes sex‐dependent disruptions of OX2 receptor signalling/function, which may have implications for choice of hypnotic therapeutics in tauopathies.
Acetazolamide and topiramate lower intracranial pressure through differential mechanisms: The effect of acute and chronic administration
Authors: Westgate Connar Stanley James , Kamp‐Jensen Christina , Israelsen Ida Marchen Egerod , Toft‐Bertelsen Trine , Wardman Jonathan Henry , Jensen Christian Ahm , Styrishave Bjarne , MacAulay Nanna , Jensen Rigmor Højland , Eftekhari Sajedeh
Published: August 2023

Background and Purpose

Diseases of raised intracranial pressure (ICP) cause severe morbidity and mortality. Multiple drugs are utilised to lower ICP including acetazolamide and topiramate. However, the evidence for their use is unclear. We aimed to assess the ICP modulatory effects and molecular effects at the choroid plexus (CP) of acetazolamide and topiramate.

Experimental Approach

Female rats were implanted with telemetric ICP probes for physiological, freely moving 24/7 ICP recordings. Randomised cross‐over studies were performed, where rats received acute (24 h) high doses of acetazolamide and topiramate, and chronic (10 days) clinically equivalent doses of acetazolamide and topiramate, all via oral gavage. Cerebrospinal fluid (CSF) secretion assays, and RT‐qPCR and western blots on in vitro and in vivo CP, were used to investigate drug actions.

Key Results

We demonstrate that acetazolamide and topiramate achieved maximal ICP reduction within 120 min of administration, and in combination doubled the ICP reduction over a 24‐h period. Chronic administration of acetazolamide or topiramate lowered ICP by 25%. Topiramate decreased CSF secretion by 40%. Chronic topiramate increased the gene expression of Slc12a2 and Slc4a10 and protein expression of the sodium‐dependent chloride/bicarbonate exchanger (NCBE), whereas chronic acetazolamide did not affect the expression of assessed genes.

Conclusions and Implications

Acetazolamide and topiramate are effective at lowering ICP at therapeutic levels. We provide the first evidence that topiramate lowers CSF secretion and that acetazolamide and topiramate may lower ICP via distinct molecular mechanisms. Thus, the combination of acetazolamide and topiramate may have utility for treating raised ICP.
A novel in‐frame deletion in MYOT causes an early adult onset distal myopathy
Authors: Guglielmi Valeria , Pancheri Elia , Cannone Elena , Nigro Vincenzo , Malatesta Manuela , Vettori Andrea , Giorgetti Alejandro , Torella Annalaura , Aurino Stefania , Cisterna Barbara , Marchetto Giulia , Tomelleri Giuliano , Tonin Paola , Schiavone Marco , Vattemi Gaetano
Published: August 2023

Missense mutations in MYOT encoding the sarcomeric Z‐disk protein myotilin cause three main myopathic phenotypes including proximal limb‐girdle muscular dystrophy, spheroid body myopathy, and late‐onset distal myopathy. We describe a family carrying a heterozygous MYOT deletion (Tyr4_His9del) that clinically was characterized by an early‐adult onset distal muscle weakness and pathologically by a myofibrillar myopathy (MFM). Molecular modeling of the full‐length myotilin protein revealed that the 4‐YERPKH‐9 amino acids are involved in local interactions within the N‐terminal portion of myotilin. Injection of in vitro synthetized mutated human MYOT RNA or of plasmid carrying its cDNA sequence in zebrafish embryos led to muscle defects characterized by sarcomeric disorganization of muscle fibers and widening of the I‐band, and severe motor impairments. We identify MYOT novel Tyr4_His9 deletion as the cause of an early‐onset MFM with a distal myopathy phenotype and provide data supporting the importance of the amino acid sequence for the structural role of myotilin in the sarcomeric organization of myofibers.
Cleft closure (the Bascom cleft lift) for 714 patients—treatment of choice for complex and recurrent pilonidal disease (a cohort study)
Authors: Ojo Dotun , Flashman Karen , Thomas Greg , Tozer Phil , Senapati Asha
Published: August 2023

Aim

Pilonidal disease is a benign condition that affects mainly the young. In existing literature, there is no consensus for best treatment, with multiple operative techniques described, some complex, resulting in a high proportion of failure and/or morbidity. The cleft closure (or cleft lift) described by Bascom and Bascom (Arch Surg, 137, 2002, 1146−50), by comparison, is a simple operation, resulting in healing in the majority and good cosmesis.

Method

This is a single surgeon series, with the aim of evaluating outcomes for consecutive patients who underwent cleft closure surgery at two centres (St Mark's Hospital, London, and Queen Alexandra Hospital, Portsmouth) between 1995 and 2021 for either extensive, complex or recurrent pilonidal disease. Primary study outcomes that were measured included rate of primary healing, time to complete healing and rate of recurrence.

Results

Some 714 patients had a cleft closure of whom 656 had documented follow‐up. Primary healing occurred in 60.7% (n = 398) rising to 88.5% by 12 weeks (n = 562) and 91.8% by 16 weeks. The remaining patients healed over the following weeks with only 19 wounds failing to heal completely (3%), requiring further surgery to achieve healing. After complete healing 5.3% of patients developed recurrent disease at a median of 12 months.

Conclusion

Cleft closure is an effective operation for pilonidal disease. Overall, 97% of patients healed without further surgery. A 3% failure rate and 5.3% recurrence rate were observed. This technique could be considered as an alternative procedure to complex flaps or midline excision, in extensive, recurrent and unhealed pilonidal disease.
NCAPG stimulates lung adenocarcinoma cell stemness through aerobic glycolysis
Authors: Zhang Zuwang , Qi Dongdong , Liu Xun , Kang Poming
Published: August 2023

Background

Cancer stem cells are pivotal in cancer progression and therapy, including lung adenocarcinoma (LUAD). High NCAPG level is implicated in malignant tumorigenesis, but investigations on NCAPG and LUAD stem cells are warranted. Hence, projecting the impact of NCAPG on cell stemness and the targeted therapy for LUAD is of the essence.

Methods

Bioinformatics analyzed NCAPG expression in LUAD tissues. qRT‐PCR assayed NCAPG expression in LUAD cells. CCK‐8 assessed cell viability and cell sphere‐forming assay measured sphere‐forming ability. Western blot assessed expression of stem cell‐related markers (CD133, CD44, Oct‐4) and specific genes (HK2, PKM2, LDHA) related to glycolysis metabolism pathway. Cellular glycolytic capacity was assayed by glycolytic metabolites pyruvic acid, lactate, citrate, and malate assay kits, and extracellular acidification rate and oxygen consumption rate analyzers.

Results

NCAPG was upregulated in LUAD and enriched in the aerobic glycolysis pathway, and its expression was positively correlated with that of glycolytic marker genes. Cell function assays revealed that NCAPG stimulated proliferation, stemness, and glycolytic activity of LUAD cells. Rescue experiments unveiled that 2‐DG (glycolysis inhibitor) was able to reverse the stimulative impact of NCAPG overexpression on proliferation, stemness, and glycolytic activity of LUAD cells.

Conclusion

NCAPG stimulated LUAD cell stemness through activation of glycolysis pathway. NCAPG may be possible biomarker for diagnosis and target for treatment of LUAD.
Topics of questions and community interaction in social Q&A during the COVID‐19 pandemic
Authors: Fu Hengyi , Oh Sanghee
Published: August 2023

Background

Considering social distancing requirements and isolation during the COVID‐19 pandemic and the widespread health mis/disinformation on social media, filling the pandemic‐related information gap is critical.

Objectives

This study explored COVID‐19‐related question topics, topic correlation, evolving trends, and community interactions by leveraging data from a health question‐answering (Q&A) community (public and health professionals) over a 2‐year period.

Methods

A total of 828 questions were collected and manually reviewed from a health Q&A and classified into 2492 codes. Question topic correlations, trends, and community interactions were generated using different statistical techniques.

Results

Thirty‐seven topics were identified, and strong topic correlations were observed between the cognitive layer and other layers. These topics changed as the pandemic developed. Community interaction analyses revealed topics that were popular but received comparatively fewer responses.

Discussion

The findings could illuminate the dynamic changes in people's interests and concerns related to COVID‐19 and their experiences of exchanging information in social Q&A communities.

Conclusion

This study examined the practical significance of understanding topics of interest during a pandemic. The findings can inform the design of social health Q&A platforms that could reduce the risks of misinformation and disinformation.
Effectiveness of family interventions for patients with schizophrenia: A systematic review and meta‐analysis
Authors: Kim Sin‐Hyang , Park Sihyun
Published: August 2023

The family is the primary caregiver for most patients with schizophrenia, and their roles are essential in patients' illness trajectories and outcomes. Due to this, various family interventions for schizophrenia have been developed and applied to the relatives who take care of their family members with schizophrenia. This study examined the effectiveness of existing family interventions for schizophrenia in achieving their target outcomes at both the family and patient levels by utilizing a systematic review and meta‐analysis. Combinations of terms were used to search for relevant studies from the databases. Thirty‐seven randomized controlled trials that met the inclusion criteria were included in the analysis. Based on the pooled result of the included studies, the programmes significantly improved the targeted outcomes with large effect size. The programmes' impacts on family‐related outcomes were higher than those on patients. Among the targeted outcomes, patients' treatment satisfaction and adherence and family caregivers' mental health were the most remarkable outcomes that had improved from the included programmes. Conversely, outcomes related to family relationships, caregiving experiences, perceived social support of family caregivers, and patients' medication use did not see significant improvements. The programmes delivered to individual family units and only to the family caregivers were more effective than those delivered to groups of caregivers and caregivers and patients together, respectively. Programme‐focused interventions were more effective than emotion‐focused ones. Based on these findings, an in‐home visiting nurse programme or advanced technology is suggested when applying family interventions for schizophrenia in practice.
Association between diabetic retinopathy and diabetic foot ulcer in patients with diabetes: A meta‐analysis
Authors: Li Ziye , Wei Jing , Lu Song
Published: August 2023

This study aimed to explore the relationship between diabetic retinopathy (DR) and diabetic foot ulcers (DFUs) to provide evidence for the prevention of diabetic complications. PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang Data databases were searched from their inception until March 2023 for studies on the relationship between DR and DFU. Two researchers independently screened the literature and extracted data according to the inclusion and exclusion criteria. The meta‐analysis was performed using the RevMan 5.3 software. Eleven articles referring to 10 208 patients were included, of whom 2191 patients had DFU and 8017 patients did not have DFU. The meta‐analysis results showed that DR significantly increased the incidence of DFU (47.94% vs. 16.38%; OR, 4.13; 95% CI, 2.33–7.33; p < 0.001). The results of this study suggest that patients with DR have a higher risk of developing DFU, highlighting the importance of regular screening for these two complications to prevent serious adverse outcomes of diabetes. However, further high‐quality studies are required to validate the conclusions of the present study.
Elevated serum uric acid is a risk factor for progression to prediabetes in Japanese women: A 5‐year retrospective chort study
Authors: Shimodaira Masanori , Minemura Yu , Nakayama Tomohiro
Published: August 2023

Aims/Introduction

The association between serum uric acid (SUA) levels and prediabetes risk remains poorly understood. The aim of this longitudinal retrospective study was to evaluate the association between SUA levels and prediabetes progression in Japanese individuals through sex‐specific analysis.

Materials and Methods

We enrolled 20,743 participants (11,916 men and 8,827 women) who underwent annual medical health checkups in 2017 (baseline) and 2022. None of the participants had diabetes and prediabetes or were taking SUA‐lowering medications at baseline. Participants were divided into four groups according to the quartiles of SUA levels at baseline. Multivariable‐adjusted Cox regression analysis was conducted to examine the risk of prediabetes progression. In addition, multivariate restricted cubic spline analysis was conducted to investigate the dose–response risk.

Results

In women, compared with the lowest SUA quartile (Q1) group, the adjusted hazard ratios (95% confidence intervals) of prediabetes in the Q2, Q3, and Q4 groups were 1.03 (0.86–1.25), 1.41 (1.18–1.68), and 1.55 (1.30–1.84), respectively. However, in men, no significant association in the risk of prediabetes was found across quartiles of SUA. Furthermore, in women, restricted cubic spline analysis revealed the dose–response relationship between SUA and progression to prediabetes.

Conclusions

The results indicate that elevated serum SUA levels might be positively and independently associated with an increased risk of progression to prediabetes in Japanese women.
Genetic, electrophysiological, and pathological studies on patients with SCN9A‐related pain disorders
Authors: Yuan Jun‐Hui , Cheng Xiaoyang , Matsuura Eiji , Higuchi Yujiro , Ando Masahiro , Hashiguchi Akihiro , Yoshimura Akiko , Nakachi Ryo , Mine Jun , Taketani Takeshi , Maeda Kenichi , Kawakami Saori , Kira Ryutaro , Tanaka Shoko , Kanai Kazuaki , Dib‐Hajj Fadia , Dib‐Hajj Sulayman D. , Waxman Stephen G. , Takashima Hiroshi
Published: August 2023

Background and Aims

Voltage‐gated sodium channel Nav1.7, encoded by the SCN9A gene, has been linked to diverse painful peripheral neuropathies, represented by the inherited erythromelalgia (EM) and paroxysmal extreme pain disorder (PEPD). The aim of this study was to determine the genetic etiology of patients experiencing neuropathic pain, and shed light on the underlying pathogenesis.

Methods

We enrolled eight patients presenting with early‐onset painful peripheral neuropathies, consisting of six cases exhibiting EM/EM‐like disorders and two cases clinically diagnosed with PEPD. We conducted a gene‐panel sequencing targeting 18 genes associated with hereditary sensory and/or autonomic neuropathy. We introduced novel SCN9A mutation (F1624S) into a GFP‐2A‐Nav1.7rNS plasmid, and the constructs were then transiently transfected into HEK293 cells. We characterized both wild‐type and F1624S Nav1.7 channels using an automated high‐throughput patch‐clamp system.

Results

From two patients displaying EM‐like/EM phenotypes, we identified two SCN9A mutations, I136V and P1308L. Among two patients diagnosed with PEPD, we found two additional mutations in SCN9A, F1624S (novel) and A1632E. Patch‐clamp analysis of Nav1.7‐F1624S revealed depolarizing shifts in both steady‐state fast inactivation (17.4 mV, p < .001) and slow inactivation (5.5 mV, p < .001), but no effect on channel activation was observed.

Interpretation

Clinical features observed in our patients broaden the phenotypic spectrum of SCN9A‐related pain disorders, and the electrophysiological analysis enriches the understanding of genotype–phenotype association caused by Nav1.7 gain‐of‐function mutations.
Potential role of inflammaging mediated by the complement system in enlarged facial pores
Authors: Qiu Wei , Chen Feng , Feng Xiaoyue , Shang Jianli , Luo Xingyi , Chen Yong
Published: August 2023

Background

Enlarged facial pores are a common cosmetic concern of the skin, rather than a disease, and have not received much attention from dermatologists in recent years. Consequently, progress in understanding their pathogenesis has been limited, and current cosmetic solutions have limitations. Given that the complement system has regained interest as a key player in chronic inflammatory skin conditions, various mechanisms involving this system are being investigated.

Objective

We aimed to shed light on the mechanism underlying enlarged facial pores by examining the role of the complement system in skin.

Methods

We conducted a comprehensive literature search utilizing various academic databases including PubMed, Web of Science, and Google Scholar. Employing keywords such as "complement system," "inflammation," "facial pores," "enlarged," and "mechanisms," we compiled a selection of relevant studies. These studies provided a comprehensive understanding of the intricate mechanisms underlying the relationship between the "complement system" and "inflammation" within the context of facial pore enlargement.

Results

Our findings suggest that inflammaging mediated by complement activation may be a critical player in the formation of enlarged facial pores. Specifically, overactivation of the complement system leading to the accumulation of complement fragments could be a major contributor to this process. Notably, the complement system in skin may be involved in a range of skin issues, including aging.

Conclusion

Modulating the complement system presents a promising avenue for future research in improving skin health. Further basic and clinical research is necessary to validate these findings, but we hope that this study can serve as a theoretical foundation for the development of targeted cosmetics.
Minimal clinically important difference of the Functional Living Index‐Emesis in patients with gynecological malignant tumor: A post hoc analysis of a single‐arm study
Authors: Fan Tingting , Luo Caifeng
Published: August 2023

Aim

This study aimed to explore the impact of minimum clinically important difference (MCID) of the Functional Living Index‐Emesis (FLIE) in patients with gynecologic malignancies.

Method

This post hoc analysis included patients with gynecological malignant tumors in the Department of Oncology of our hospital between October 2020 and October 2021.

Results

A total of 149 patients (aged 50.05 ± 12.24 years) were included. Most of the patients were married (75.8%), lived in the city (60.4%), and had a history of motion sickness (75.8%). The degree of nausea (9.00 [0.00, 16.00] vs. 30.00 [16.00, 48.00], P < 0.001) and vomiting (9.00 [0.00, 16.00] vs. 30.00 [16.00, 48.00], P < 0.001) were significantly improved after treatment. Taking the options in the scale as the subjective anchor, the MCID of FLIE for nausea and vomiting were 28.5 and 29 in anchor‐based analysis, respectively. In the distribution‐based analysis, the MCID of FLIE for nausea and vomiting were 2.41, 6.04, and 9.66; and 2.31, 5.78, and 9.24 in effect size of 0.2, 0.5, and 0.8, respectively.

Conclusion

The MCID of FLIE for nausea and vomiting in patients with gynecological malignant tumors was 28.5 and 29 in the anchor‐based analysis, with higher specificity, and 6.04 and 5.78 in the distribution‐based analysis, with higher sensitivity. The development of the MCID scale might be used to interpret the clinical significance of chemotherapy‐induced nausea and vomiting in patients with gynecological malignancies and help to calculate the sample size for future clinical trials.
Effects of mixed fibres and essential oils blend on growth performance and intestinal barrier function of piglets challenged with enterotoxigenic Escherichia coli K88
Authors: Liang Chan , Fu Runqi , Chen Daiwen , Tian Gang , He Jun , Zheng Ping , Mao Xiangbing , Yu Bing
Published: August 2023

This study was to evaluate the effects of supplementing mixed dietary fibres (MDF) and essential oils blend (EOB) either alone or in combination on growth performance and intestinal barrier function in weaned piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC). Forty‐two piglets (28 days old) were randomly allocated into six treatments in a 25‐day experiment, and fed the basal diet (CON or ETEC) either with antibiotics (AT), MDF, EOB or MDF + EOB. On Day 22 of the experiment, pigs in CON and challenged groups (ETEC, AT, MDF, EOB and MDF + EOB) were orally administered sterile saline and ETEC containing 6 × 1010 CFU/kg body weight respectively. On Day 26, all pigs were euthanized to collect samples. Before ETEC challenge, piglets in MDF and EOB had lower diarrhoea incidence (p < 0.01) than others. After ETEC challenge, piglets in ETEC had lower average daily gain and higher diarrhoea incidence (p < 0.05) than those of CON. Furthermore, compared to CON, ETEC group increased the serum lipopolysaccharide concentration and diamine oxidase activity, and decreased mRNA levels of genes relating to barrier function (aquaporin 3, AQP3; mucin1, MUC1; zonula occludens‐1, ZO‐1; Occludin), and increased the concentration of cytokines (interleukin‐1β/4/6/10, IL‐1β/4/6/10) and secretory immunoglobulin A (sIgA) in jejunal mucosa (p < 0.05). However, these deleterious effects induced by ETEC were partly alleviated by MDF, EOB, MDF + EOB and AT. Additionally, compared to ETEC group, MDF increased Bifidobacterium abundance in cecal digesta and butyrate concentration in colonic digesta (p < 0.05). Also, EOB improved propionate concentration in cecal digesta, and MDF + EOB decreased IL‐10 concentration in jejunal mucosa (p < 0.05) compared with ETEC. Conclusively, MDF and EOB either alone or in combination can improve growth performance and alleviate diarrhoea via improving intestinal barrier function of piglets after ETEC challenge, and all may serve as potential alternatives to AT for piglets.
Short‐term outcome and complications following cutaneous reconstruction using cranial superficial epigastric axial pattern flaps in dogs: six cases (2008‐2022)
Authors: Gaudio E. , Aertsens A. , Field E. , Hattersley R. , Baines S.
Published: August 2023

Objectives

To investigate short‐term outcome and complications following the use of the cranial superficial epigastric axial pattern flap to reconstruct cutaneous defects in dogs.

Materials and Methods

Medical records from dogs undergoing reconstructive surgery between 2008 and 2022 by means of cranial superficial epigastric axial pattern flap were reviewed. Data on signalment, reason for reconstruction, defect size, flap healing, post‐operative complications and need for revision surgery were collected.

Results

Six dogs were included in the study. Indications for reconstruction included neoplasia (4/6), skin necrosis due to vehicular trauma (1/6) and dog bite (1/6). Postoperative complications occurred in 50% of the patients and included seroma (1/6), bruising (2/6) and necrosis of the distal portion of the flap (2/6), with two dogs developing concurrent complications. One dog required open wound management and additional surgery. Overall outcome was scored excellent in three, good in two, and fair in one dog.

Clinical Significance

Despite the relatively high complication rate, most of the complications were deemed minor and could be managed conservatively. Eventually, all wounds healed completely and only one flap required revision surgery.
Cascade of care among people with hepatitis B in New South Wales, Australia
Authors: Shah Syed Hassan Bin Usman , Valerio Heather , Hajarizadeh Behzad , Matthews Gail , Alavi Maryam , Dore Gregory J.
Published: August 2023

Hepatitis B virus (HBV) care cascade characterisation is important for monitoring HBV elimination progress. This study evaluated care cascade and factors associated with HBV DNA testing and treatment in New South Wales, Australia. HBV care cascade were determined through linkage of HBV notifications (1993–2017) to Medicare and pharmaceutical benefits schemes (2010–2018). Timely HBV DNA testing was within 4 weeks of HBV notification. Multivariate Cox proportional hazards regression evaluated factors associated with HBV DNA testing and treatment. Among 15,202 people with HBV notification, 10,479 (69%) were tested for HBV DNA. A total of 3179 (21%) initiated HBV treatment. HBV DNA testing was more likely among age ≥45 years (adjusted hazard ratio [aHR] 1.07, 95% CI: 1.02, 1.12), hepatocellular carcinoma (HCC) (aHR 1.23, 95% CI: 1.01, 1.50), coinfection (aHR 1.61, 95% CI: 1.23, 2.09), later notification (2014–2017) (aHR 1.21, 95% CI: 1.16, 1.26) and less likely among females (aHR 0.95, 95% CI: 0.91, 0.99), history of alcohol use disorder (AUD) (aHR 0.77, 95% CI: 0.66, 0.89), HCV coinfection (aHR .62, 95% CI: 0.55, 0.70) and Indigenous peoples (aHR 0.84, 95% CI: 0.71, 0.98). HBV treatment was associated with age ≥45 years (aHR 1.35, 95% CI: 1.24, 1.48), decompensated cirrhosis (aHR 2.07, 95% CI: 1.62, 2.65), HCC (aHR 2.96, 95% CI: 2.35, 3.74), HIV coinfection (aHR 4.27, 95% CI: 3.43, 5.31) and later notification (2014–2017) (aHR 1.37, 95% CI: 1.26, 1.47). HBV treatment was less likely among females (aHR 0.68, 95% CI: 0.63, 0.73) and Indigenous peoples (aHR 0.58, 95% CI: 0.42, 0.80). HBV DNA testing and treatment coverage have increased, but remain sub‐optimal among some key populations.
Predictive factors for treatment response and mortality in chronic pulmonary aspergillosis
Authors: Kosmidis Chris , Smith Holly , Mollett Guy , Harris Chris , Akili Suha , Bazaz Rohit
Published: August 2023

Objectives

Chronic pulmonary aspergillosis (CPA) is associated with significant mortality, and suboptimal antifungal treatment response. We describe predictive factors for treatment response and survival.

Methods

We retrospectively analysed clinical, serological and radiological parameters at baseline and following antifungal treatment in patients with CPA and correlated with clinical and radiological response and survival.

Results

Fifty‐nine patients were included with a mean age of 61 years. Thirty (51%) had a diagnosis of COPD. On clinical assessment at 6 months, 21 (36%) had clinically improved, 20 (34%) were clinically stable and 15 (25%) had deteriorated. Radiological improvement was observed in 30 (53%), stability in 11 (19%) and deterioration in 16 (28%). Only a lower C‐reactive protein (CRP) at baseline was associated with a favourable clinical‐radiological response. On univariate analysis, lower CRP, higher albumin, lower Aspergillus IgG and use of inhaled steroids were associated with lower mortality. An overall favourable response at 6 months was associated with lower mortality.

Conclusion

Inflammatory markers and Aspergillus IgG were predictors of mortality in CPA. This suggests that mortality in CPA is driven mainly by the chronic fungal infection itself rather than the underlying disease, therefore early optimised treatment of CPA may lead to improved outcomes.
Three‐dimensional volumetric evaluation of root resorption in maxillary anteriors following en‐masse retraction with varying force vectors – a randomized control trial
Authors: Prasanna Arvind T. R. , Ramasamy N. , Subramanian A. K. , Selvaraj A. , Siva S.
Published: August 2023

Background

Root resorption in orthodontics is associated with direction and magnitude of force application as primary etiological factors. Well‐controlled trials that utilize three‐dimensional segmentation to detect volumetric changes in tooth structure are required to assess the quantitative nature of root resorption.

Objective

To assess the severity of root resorption (RR) during retraction of maxillary anteriors with three different force vectors (with and without skeletal anchorage) via cone‐beam computed tomography (CBCT) superimpositions.

Trial Design

Three‐arm parallel randomized clinical trial (RCT).

Materials and Methods

Forty‐two (16 males, 26 females) patients, (17–28 years), in permanent dentition with bimaxillary protrusion were randomly allocated to three groups of 14 patients each using block randomization (1:1:1 ratio) and allocation concealment. En‐masse anterior retraction post first premolar extractions was carried out with modified force vectors in the three groups based on anchorage type [Molar, Mini‐implant and Infrazygomatic crest (IZC) bone screws]. Volumetric root loss and linear dimensional changes were blindly assessed on initial (T0) and final (T1, end of space closure) CBCT scans. Normality distribution of values was done using Shapiro–Wilk's test. ANOVA and Post‐hoc Tukey HSD test were done to compare measurements between groups at significance levels (P < .05).

Results

Forty patients were analysed (14, 14, and 12 in three groups). Significant volumetric loss was noted in all groups. Central incisors demonstrated a significant reduction in IZC group (81.5 ± 21.1 mm3) compared to conventional (50.1 ± 26.5 mm3) and mini‐implant groups (76.1 ± 27.6 mm3). Canines demonstrated a significant reduction in mini‐implant group (108.9 ± 33.9 mm3) compared to conventional (68.8 ± 42.5 mm3) and IZC groups (103.1 ± 29.1 mm3). Regarding linear parameters, central incisors and canines revealed significant root length reduction in both skeletal anchorage groups. Lateral incisors showed no significant changes between groups.

Conclusions

Intrusive force vectors generated during skeletally anchored retraction can predispose anteriors to an increased risk of resorption. Greater loss of root volume was noted in the centrals and canines when retracted with skeletal anchorage.

Limitations

Small sample size and variations during CBCT acquisition.

Harms

Low‐dose CBCT scans were taken at T0 and T1 treatment intervals.
The role of environmental stress in fruit pigmentation
Authors: Espley Richard V. , Jaakola Laura
Published: August 2023

For many fruit crops, the colour of the fruit outwardly defines its eating quality. Fruit pigments provide reproductive advantage for the plant as well as providing protection against unfavourable environmental conditions and pathogens. For consumers these colours are considered attractive and provide many of the dietary benefits derived from fruits. In the majority of species, the main pigments are either carotenoids and/or anthocyanins. They are produced in the fruit as part of the ripening process, orchestrated by phytohormones and an ensuing transcriptional cascade, culminating in pigment biosynthesis. Whilst this is a controlled developmental process, the production of pigments is also attuned to environmental conditions such as light quantity and quality, availability of water and ambient temperature. If these factors intensify to stress levels, fruit tissues respond by increasing (or ceasing) pigment production. In many cases, if the stress is not severe, this can have a positive outcome for fruit quality. Here, we focus on the principal environmental factors (light, temperature and water) that can influence fruit colour.
The role of status diversity in the innovative performance of R&D teams
Authors: Liu Zhiqiang , Ozer Muammer , Zhou Kong
Published: August 2023

Past research on team diversity has used diversity attributes that are primarily related to team members' either social (e.g., age, ethnicity, and gender) or information‐processing (e.g., educational and functional background) characteristics. In this paper, we focus on status diversity, which is a relatively understudied but highly‐prevalent diversity attribute. However, team status diversity can be highly subjective and complex. Accordingly, we propose and test a curvilinear relationship between status diversity and team innovation through team integration. Furthermore, we study how empowering leadership moderates this indirect curvilinear relationship. The results from 61 R&D teams with 355 team members suggested that status diversity had an inverted U‐shaped relationship with team integration, which then had a positive relationship with team innovation. Moreover, they showed that empowering leadership played a dual role in moderating this curvilinear relationship. More specifically, while it facilitated the positive relationship between the low‐to‐medium degrees of status diversity and team integration, it exacerbated the negative relationship between the medium‐to‐high degrees of status diversity and team integration.
Properties of given and detected unbounded solutions to a class of chemotaxis models
Authors: Columbu Alessandro , Frassu Silvia , Viglialoro Giuseppe
Published: August 2023

This paper deals with unbounded solutions to a class of chemotaxis systems. In particular, for a rather general attraction–repulsion model, with nonlinear productions, diffusion, sensitivities, and logistic term, we detect Lebesgue spaces where given unbounded solutions also blow up in the corresponding norms of those spaces; subsequently, estimates for the blow‐up time are established. Finally, for a simplified version of the model, some blow‐up criteria are proved.

More precisely, we analyze a zero‐flux chemotaxis system essentially described as

The problem is formulated in a bounded and smooth domain Ω of , with , for some , , , and with . A sufficiently regular initial data is also fixed.

Under specific relations involving the above parameters, one of these always requiring some largeness conditions on ,

we prove that any given solution to (), blowing up at some finite time becomes also unbounded in ‐norm, for all ;

we give lower bounds T (depending on ) of for the aforementioned solutions in some ‐norm, being ;

whenever , we establish sufficient conditions on the parameters ensuring that for some u0 solutions to () effectively are unbounded at some finite time.

Within the context of blow‐up phenomena connected to problem (), this research partially improves the analysis in Wang et al. (J Math Anal Appl. 2023;518(1):126679) and, moreover, contributes to enrich the level of knowledge on the topic.
Determinants of intangible capital investment in Vietnam: A firm‐level analysis
Authors: Li Qing , Vo Long Hai
Published: August 2023

Intangible capital is an important growth driver in the modern knowledge‐based and innovation‐driven economy. While there seems to be sufficient support for the role of intangible capital from developed economies, evidence from fast‐growing developing countries is much more limited. This paper explores the heterogeneous pattern and potential determinants of firm‐level intangible capital investment in Vietnam. We found that firm size, human capital, and information and communication technology increase the likelihood to invest in intangible capital. Additionally, an inverted‐U shaped relation is identified between market competition and intangible capital investment: Moderate levels of market competition induce firms in Vietnam to invest more in innovative activities, but the effect of stronger competition diminishes.
Building the Business Case for Industry 4.0
Authors: O’Heir Jeff
Published: August 2023

Manufacturers are speeding Industry 4.0 adoption as they seek to leverage the improved resiliency, productivity, and agility delivered by digital technologies over the last three years. Lower acquisition costs, ease-of-use, clearer return on investment, a young digital-native workforce eager to explore new solutions, agnostic operating software, and managers less adverse to the risk of bringing on new solutions will continue to drive adoption.
Collaborations that Forge the Future
Authors: Curran Scott , Lavertu Tom , Som Sibendu
Published: August 2023

A recent research initiative promoted with federal funding provides an excellent example of how ASME continues to push the boundary toward cleaner, more efficient transportation.
Tribo-Dynamic Performance of Newly Developed Environmentally Friendly Lubricating Greases Containing Nano-CaCO3
Authors: Saxena Ankit , Kumar Deepak , Tandon Naresh
Published: August 2023

The present study explores the performance of novel vegetable oil–based greases containing nano-CaCO3 as an additive. A series of greases with varying nanoparticle concentrations (0–4% w/w) are evaluated on a four-ball tester machine under a standard tribological test (ASTM D2266) and simultaneously in a rolling bearing at various speeds and loads against two commercial greases as the benchmark. The vibrations and shock pulse measurements are recorded to assess the bearing performance. The tribo-dynamic investigation suggests that the eco-friendly nano-greases are at par with the commercial ones; performance varies with the nanoparticle concentration. Under the tribological test, the third-body action of nanoparticles seems to increase friction, while the interfacial deposition (physisorption) of nano-CaCO3 and nano-CaO decreases wear. Under the bearing test, the rolling effect of nanoparticles seems to influence vibrations, while their entrainment in the contact zone governs the carpet values. The nano-grease containing 4% nano-CaCO3 performs best under both assessments, displaying great prospects of a sustainable and potential alternative to existing environmentally unfriendly greases.
Effects of A Single Balance Training Session on Neural Excitability in Individuals With Chronic Ankle Instability
Authors: Chung Sunghoon , Rodriguez Avery , Alijanpour Elham , McCann Ryan S.
Published: August 2023

Context: Individuals with chronic ankle instability (CAI) demonstrate reduced spinal reflex modulation and corticospinal excitability of the soleus, which may contribute to decreased balance performance. Objective: To determine the effects of a single session of balance training on Spinal-reflexive excitability modulation and corticospinal excitability in those with CAI. Design: Randomized controlled trials. Setting: Research laboratory. Participants: Thirty participants with CAI were randomly assigned to the balance training (BAL) or control (CON) group. Main Outcome Measures: Modulation of soleus spinal-reflexive excitability was measured by calculating relative change in normalized Hoffmann reflexes (ratio of the H-reflex to the M-wave) from prone to single-leg standing. Corticospinal excitability was assessed during single-leg stance using transcranial magnetic stimulation, outcomes of which included active motor threshold (AMT), motor evoked potential, and cortical silent period (CSP). Balance performance was measured with center of pressure velocity in anterior to posterior and medial to lateral directions. Separate 2 × 2 repeated-measures analyses of variance were employed to determine the effect of group (BAL and CON) and time (baseline and posttraining) on each dependent variable. Results: There were significant group by time interactions in the modulation of soleus spinal-reflexive excitability (F1,27 = 4.763, P = .04); CSP at 100% AMT (F1,27 = 4.727, P = .04); and CSP at 120% AMT (F1,27 = 16.057, P < .01). A large effect size suggests increased modulation of spinal-reflexive excitability (d = 0.81 [0.03 to 1.54]) of the soleus in BAL compared with CON at posttest, while CSP at 100% (d = 0.95 [0.17 to 1.70]) and 120% AMT (d = 1.10 [0.29 to 1.84]) was reduced in BAL when compared with CON at posttest. Conclusion: After a single session of balance training, individuals with CAI initiated increases in spinal reflex modulation and corticospinal excitability of the soleus. Thus, individuals with CAI who undergo balance training exhibit positive neural adaptations that are linked to improvements in balance performance.
DeepAIR: A deep learning framework for effective integration of sequence and 3D structure to enable adaptive immune receptor analysis
Authors: Zhao Yu , He Bing , Xu Fan , Li Chen , Xu Zhimeng , Su Xiaona , He Haohuai , Huang Yueshan , Rossjohn Jamie , Song Jiangning , Yao Jianhua
Published: August 2023

Structural docking between the adaptive immune receptors (AIRs), including T cell receptors (TCRs) and B cell receptors (BCRs), and their cognate antigens are one of the most fundamental processes in adaptive immunity. However, current methods for predicting AIR-antigen binding largely rely on sequence-derived features of AIRs, omitting the structure features that are essential for binding affinity. In this study, we present a deep learning framework, termed DeepAIR, for the accurate prediction of AIR-antigen binding by integrating both sequence and structure features of AIRs. DeepAIR achieves a Pearson’s correlation of 0.813 in predicting the binding affinity of TCR, and a median area under the receiver-operating characteristic curve (AUC) of 0.904 and 0.942 in predicting the binding reactivity of TCR and BCR, respectively. Meanwhile, using TCR and BCR repertoire, DeepAIR correctly identifies every patient with nasopharyngeal carcinoma and inflammatory bowel disease in test data. Thus, DeepAIR improves the AIR-antigen binding prediction that facilitates the study of adaptive immunity.
Why the 2022 Po River drought is the worst in the past two centuries
Authors: Montanari Alberto , Nguyen Hung , Rubinetti Sara , Ceola Serena , Galelli Stefano , Rubino Angelo , Zanchettin Davide
Published: August 2023

The causes of recent hydrological droughts and their future evolution under a changing climate are still poorly understood. Banking on a 216-year river flow time series at the Po River outlet, we show that the 2022 hydrological drought is the worst event (30% lower than the second worst, with a six-century return period), part of an increasing trend in severe drought occurrence. The decline in summer river flows (−4.14 cubic meters per second per year), which is more relevant than the precipitation decline, is attributed to a combination of changes in the precipitation regime, resulting in a decline of snow fraction (−0.6% per year) and snowmelt (−0.18 millimeters per day per year), and to increasing evaporation rate (+0.013 cubic kilometers per year) and irrigated areas (100% increment from 1900). Our study presents a compelling case where the hydrological impact of climate change is exacerbated by local changes in hydrologic seasonality and water use.
Distinct roles of the orbitofrontal cortex, ventral striatum, and dopamine neurons in counterfactual thinking of decision outcomes
Authors: Yun Mengxi , Nejime Masafumi , Kawai Takashi , Kunimatsu Jun , Yamada Hiroshi , Kim HyungGoo R. , Matsumoto Masayuki
Published: August 2023

Individuals often assess past decisions by comparing what was gained with what would have been gained had they acted differently. Thoughts of past alternatives that counter what actually happened are called “counterfactuals.” Recent theories emphasize the role of the prefrontal cortex in processing counterfactual outcomes in decision-making, although how subcortical regions contribute to this process remains to be elucidated. Here we report a clear distinction among the roles of the orbitofrontal cortex, ventral striatum and midbrain dopamine neurons in processing counterfactual outcomes in monkeys. Our findings suggest that actually gained and counterfactual outcome signals are both processed in the cortico-subcortical network constituted by these regions but in distinct manners and integrated only in the orbitofrontal cortex in a way to compare these outcomes. This study extends the prefrontal theory of counterfactual thinking and provides key insights regarding how the prefrontal cortex cooperates with subcortical regions to make decisions using counterfactual information.
Genetically targeted chemical assembly of polymers specifically localized extracellularly to surface membranes of living neurons
Authors: Zhang Anqi , Loh Kang Yong , Kadur Chandan S. , Michalek Lukas , Dou Jiayi , Ramakrishnan Charu , Bao Zhenan , Deisseroth Karl
Published: August 2023

Multicellular biological systems, particularly living neural networks, exhibit highly complex organization properties that pose difficulties for building cell-specific biocompatible interfaces. We previously developed an approach to genetically program cells to assemble structures that modify electrical properties of neurons in situ, opening up the possibility of building minimally invasive cell-specific structures and interfaces. However, the efficiency and biocompatibility of this approach were challenged by limited membrane targeting of the constructed materials. Here, we design a method for highly localized expression of enzymes targeted to the plasma membrane of primary neurons, with minimal intracellular retention. Next, we show that polymers synthesized in situ by this approach form dense extracellular clusters selectively on the targeted cell membrane and that neurons remain viable after polymerization. Last, we show generalizability of this method across a range of design strategies. This platform can be readily extended to incorporate a broad diversity of materials onto specific cell membranes within tissues and may further enable next-generation biological interfaces.
Mitochondrial evolution: Gene shuffling, endosymbiosis, and signaling
Authors: Raval Parth K. , Martin William F. , Gould Sven B.
Published: August 2023

Genes for cardiolipin and ceramide synthesis occur in some alphaproteobacterial genomes. They shed light on mitochondrial origin and signaling in the first eukaryotic cells.