bluuebunny/crossref_metadata_2025 huggingface dataset:
Humeral Head Reconstruction With Osteochondral Allograft: Bone Plug Optimization for Hill-Sachs Lesions Using CT-Based Computer Modeling Analysis
Authors: Ganokroj Phob , Hollenbeck Justin , Peebles Annalise M. , Brown Justin R. , Hanson Jared A. , Whalen Ryan J. , Golijanin Petar , Provencher CAPT Matthew T.
Published: September 2023

Background:

Engaging Hill-Sachs lesions (HSLs) pose a significant risk for failure of surgical repair of recurrent anterior shoulder instability. Reconstruction with fresh osteochondral allograft (OCA) has been proposed as a treatment for large HSLs.

Purpose:

To determine the optimal characteristics of talus OCA bone plugs in a computer-simulated HSL model.

Study Design:

Descriptive laboratory study; Level of evidence, 6

Methods:

Included were 132 patients with recurrent anterior instability with visible HSLs; patients who had multidirectional instability or previous shoulder surgery were excluded. Three-dimensional computed tomography models were constructed, and a custom computer optimization algorithm was generated to maximize bone plug surface area at the most superior apex (superiorization) and minimize its position relative to the most medial margin of the HSL defect (medialization). The optimal number, diameter, medialization, and superiorization of the bone plug(s) were reported. Percentages of restored glenoid track width and conversion from off- to on-track HSLs after bone plug optimization were calculated.

Results:

A total of 86 patients were included in the final analysis. Off-track lesions made up 19.7% of HSLs and, of these, the mean bone plug size was 9.9 ± 1.4 mm, with 2.2 mm ± 1.7 mm of medialization and 3.3 mm ± 2.9 mm of superiorization. The optimization identified 21% of HSLs requiring 1 bone plug, 65% requiring 2 plugs, and 14% requiring 3 plugs, with a mean overall coverage of 60%. The mean width of the restored HSLs was 68%, and all off-track HSLs (n = 17) were restored to on-track. A Jenks natural-breaks analysis calculated 3 ideal bone plug diameters of 8 mm (small), 10.4 mm (medium), and 12 mm (large) in order to convert this group of HSLs to on-track.

Conclusion:

Using a custom computer algorithm, we have demonstrated the optimal talus OCA bone plug diameters for reconstructing HSLs to successfully restore the HSL track and, on average, 60% of the HSL surface area and 68% of the HSL width.

Clinical Relevance:

Reconstructing HSLs with talus OCA is a promising treatment option with excellent fit and restoration of HSLs. This study will help guide surgeons to optimize OCA bone plugs from the humeral head, femoral head, and talus for varying sizes of HSLs.
Experiences of a Novel Integrated Service for Older Adults at Risk of Frailty: A Qualitative Study
Authors: Wilson Imogen , Ukoha-kalu Blessing O , Okoeki Mabel , Clark Joseph , Boland Jason W , Pask Sophie , Nwulu Ugochinyere , Elliott-Button Helene , Folwell Anna , Johnson Miriam J , Harman Daniel , Murtagh Fliss EM
Published: September 2023

The UK has a significant and growing population of older adults with frailty and complex healthcare needs, necessitating innovative care solutions. This study aimed to explore patients’ and carers’ experiences of a novel integrated service that was set up to address the increasing healthcare needs of older people living with frailty. A qualitative study that combined free-text survey questions with in-depth interviews. This study is part of a larger non-randomized trial of the service, with evaluation of wellbeing and quality of life at baseline, 2 to 4 weeks, and 10 to 14 weeks. Patients (aged 65 and above) with an electronic Frailty Index in the severe range and their informal family carers participated in this study. Data were collected between April 2019 and March 2020. Free text survey responses and interview data were subjected to reflexive thematic analyses. Four themes were generated: the overall experience of the service; interactions within the service; treatment and interventions; and outcomes due to the service. Most participants wanted further follow-up and more extensive integration with other services. Most participants described their overall experience positively, especially the available time to address their full range of concerns, but opportunities to integrate the service more fully and to extend follow-up remain.
Deucravacitinib: A Novel TYK2 Inhibitor for the Treatment of Moderate-to-Severe Psoriasis
Authors: Kingston Paige , Blauvelt Andrew , Strober Bruce , Armstrong April W.
Published: September 2023

Background

Deucravacitinib is a first-in-class tyrosine kinase 2 (TYK2) inhibitor recently approved for the treatment of adults with moderate-to-severe plaque psoriasis.

Objective

To discuss the mechanism of action, efficacy, safety, and real-world applications of deucravacitinib for the treatment of psoriasis.

Methods

Literature on the mechanism of action of deucravacitinib is reviewed. The pivotal clinical studies and long-term extension studies for deucravacitinib are also examined.

Results

Deucravacitinib is a novel oral TYK2 inhibitor that binds to the regulatory domain of TYK2, a Janus kinase. By inhibiting TYK2, deucravacitinib interferes with signaling of IL-23, IL-12, and type I interferons, cytokines believed to play important roles in psoriasis pathogenesis. Nearly 60% of patients achieve PASI 75 at 16 weeks of treatment; efficacy improves over 24 weeks and is maintained through 2 years of continuous treatment. In a head-to-head comparison, deucravacitinib efficacy was superior to apremilast, an older yet commonly used oral PDE4 inhibitor approved for the treatment of psoriasis. Of note, patients with moderate-to-severe plaque psoriasis with concomitant involvement of the scalp, nails, and/or palms/soles demonstrated good improvement in these high impact areas. Deucravacitinib has an acceptable safety profile and is generally well-tolerated. Small increases in reactivation of herpesvirus infections, including herpes simplex outbreaks, have been reported. Tuberculosis evaluation, but no other blood tests, is recommended prior to initiation of deucravacitinib. Monitoring of triglyceride levels should be conducted for high-risk patients according to local guidelines.

Conclusion

Deucravacitinib is an effective, safe, and well-tolerated novel oral medication for adults with moderate-to-severe plaque psoriasis.
Enacting the blue economy in the Western Indian Ocean: A ‘collaborative blue economy governmentality’
Authors: Midlen Alex
Published: September 2023

The blue economy represents a new development paradigm, being promoted through multilateral institutions. I examine its emerging nature in the context of the Western Indian Ocean region of Africa. I situate the blue economy within the global sustainable development discourse and argue that it represents a form of global governmentality. I note its utopian nature and argue that discourses of utopian thought and risk act to ‘responsibilise’ States to collaborate in regional sea management in pursuit of human and environmental security goals – which I call a ‘collaborative blue economy governmentality’. I draw attention to multiple sites of resistance (‘counter conducts’) to this governmentality. These counter conducts are diverse, encompassing community resistance to development priorities, insufficient technical capacities and resources, and the material character of ocean and coastal ecosystems. I therefore characterise the blue economy as an immature governmentality, necessitating State and multilateral intervention to put in place or strengthen the governmental capacities needed to enact it. I conclude that the BE governmentality is largely of a neoliberal character, but with hints of an emergent post-neoliberal regime.
Acupoint Transcutaneous Electrical Nerve Stimulation in Hospitalized COPD Patients with Severe Dyspnoea: A Randomized Controlled Trial
Authors: Fernández-Jané Carles , Vilaró Jordi , Costa-Tutusaus Lluís
Published: September 2023

Objective

To evaluate the effect of acupuncture transcutaneous electrical nerve stimulation (acuTENS) on the reduction of dyspnoea during acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods

A multicentric randomized control trial with masked patients and evaluators was carried out. During hospitalization, AECOPD patients received 45 min of acuTENS (experimental group) or sham acuTENS (controls) daily on 5 consecutive days. The trial was conducted at the Hospital del Mar, Barcelona, and Hospital Sant Joan de Déu, Manresa (both in Spain). Dyspnoea and peak expiratory flow were measured daily from the first to fifth days. Length of stay, readmissions at 3 months and adverse events were also analysed.

Results

Finally, 19 patients with moderately to severely exacerbated COPD were included. Although some tendencies in dyspnoea during day 1 and length of hospital stay were found favouring acupuncture, no significant differences were shown between groups.

Conclusions

The acuTENS intervention was feasible#well tolerated in AECOPD patients and no important side effects were reported.
A Short-Term Safety Evaluation of Silbinol®- an Extract from Pterocarpus marsupium in Healthy Adults- a Randomized, Double-Blind, Placebo-Controlled Study
Authors: Majeed Muhammed , Nagabhushanam Kalyanam , Paulose Shaji , Mundkur Lakshmi
Published: September 2023

Background: Pterostilbene is an active molecule from the bark of the Pterocarpus marsupium tree with antioxidant and anti-inflammatory properties. Objective: This study aimed to evaluate the clinical safety of a standardized P. marsupium extract (PME) containing 90% pterostilbene (200 mg per day) in healthy adults. Methods: In a randomized, double-blind, placebo-controlled study, 60 healthy adult participants (27 males and 33 females) were randomized to receive PME-100 mg or placebo capsule twice a day for two months. The primary objectives of the study were to assess any changes in laboratory parameters, vital signs, and the occurrence of adverse events from screening to the final visit. Serum antioxidant enzyme levels were evaluated as a secondary outcome. Results: The hematological, lipid, glycemic, thyroid profiles and liver and renal functions remained within the normal range in all participants, with no difference between PME and placebo. Vital signs, including blood pressure, pulse rate, body weight, body mass index and electrocardiogram, did not reveal any significant differences between the PME and placebo groups at the beginning and end of the study. No serious adverse events were observed in any participant throughout the study period. The serum antioxidant profile was not significantly different between the treatment groups, although the glutathione levels were relatively higher in the PME group. Conclusions: Scientific evaluation of clinical safety of standardized extract is mandatory for its use as a supplement for various health benefits. The results of this study convincingly establish the safety of PME (>90% Pterostilbene) at 200 mg/day (100 mg bid) for human use. The study was approved by the Institutional Ethics Committee of BGS Global Institute of Medical Sciences & Hospital, Bangalore with the registration number CTRI/2019/08/020736.
Unsupervised home spirometryversussupervised clinic spirometry for respiratory disease: a systematic methodology review and meta-analysis
Authors: Anand Rohan , McLeese Rebecca , Busby John , Stewart Jonathan , Clarke Mike , Man William D-C. , Bradley Judy
Published: September 2023

Background:

The number of patients completing unsupervised home spirometry has recently increased due to more widely available portable technology and the COVID-19 pandemic, despite a lack of solid evidence to support it. This systematic methodology review and meta-analysis explores quantitative differences in unsupervised spirometry compared with spirometry completed under professional supervision.

Methods:

We searched four databases to find studies that directly compared unsupervised home spirometry with supervised clinic spirometry using a quantitative comparison (e.g.Bland–Altman). There were no restrictions on clinical condition. The primary outcome was measurement differences in common lung function parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)), which were pooled to calculate overall mean differences with associated limits of agreement (LoA) and confidence intervals (CI). We used the I2statistic to assess heterogeneity, the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence certainty for the meta-analyses. The review has been registered with PROSPERO (CRD42021272816).

Results:

3607 records were identified and screened, with 155 full texts assessed for eligibility. We included 28 studies that quantitatively compared spirometry measurements, 17 of which reported a Bland–Altman analysis for FEV1and FVC. Overall, unsupervised spirometry produced lower values than supervised spirometry for both FEV1with wide variability (mean difference −107 mL; LoA= −509, 296; I2=95.8%; p<0.001; very low certainty) and FVC (mean difference −184 mL, LoA= −1028, 660; I2=96%; p<0.001; very low certainty).

Conclusions:

Analysis under the conditions of the included studies indicated that unsupervised spirometry is not interchangeable with supervised spirometry for individual patients owing to variability and underestimation.
The panda-derived Lactiplantibacillus plantarum BSG201683 improves LPS-induced intestinal inflammation and epithelial barrier disruption in vitro
Authors: Zhou Yi , Duan Ling , Zeng Yan , Song Xu , Pan Kangcheng , Niu Lili , Pu Yang , Li Jiakun , Khalique Abdul , Fang Jing , Jing Bo , Zeng Dong , Shen Bairong , Ni Xueqin
Published: September 2023

Captive pandas are suffering from intestinal infection due to intestinal microbiota characterized by a high abundance of Enterobacteriaceae induced by long-term captivity. Probiotic supplements showed improvement in intestinal barrier function and inflammation. However, the effects of panda-derived probiotics on the intestinal epithelium and inflammation have not been elucidated. In the present study, lipopolysaccharide (LPS) impaired Caco-2 and RAW264.7 inflammatory models were applied to assess the protection of Lactiplantibacillus plantarum BSG201683 (L. plantarum G83) on barrier disruption and inflammation. The results showed that treatment with L. plantarum G83 significantly decreased the paracellular permeability to fluorescein isothiocyanate conjugated dextran (MW 4000, FITC-D4) after LPS induction. Meanwhile, L. plantarum G83 alleviated the reduction in tight junction (TJ) proteins and downregulated proinflammatory cytokines caused by LPS in Caco-2 cells. L. plantarum G83 also significantly decreased the expression and secretion of pro-inflammatory cytokines in LPS-induced RAW264.7 cells. In addition, the IL-10 increased in both Caco-2 and RAW264.7 cells after L. plantarum G83 treatment. The phagocytosis activity of RAW264.7 cells was significantly increased after L. plantarum G83 treatment. Toll-like receptor 4/ nuclear factor kappa-B (TLR4/NF-κB) signaling pathways were significantly down-regulated after L. plantarum G83 intervention, and the phosphorylation of NF-κB/p65 was consistent with this result. Our findings suggest that L. plantarum G83 improves intestinal inflammation and epithelial barrier disruption in vitro.
Treatment of acute mesenteric ischemia between 2010 and 2020 – a German nation-wide study
Authors: Bette Stefanie , Habeeballah Osama , Luitjens Jan H. , Kroencke Thomas , Scheurig-Muenkler Christian , Decker Josua A.
Published: September 2023

Background

Aim of this study was to analyze long-term trends of hospitalizations, treatment regimen and in-hospital mortality of in-patients with acute mesenteric ischemia (AMI) over the past decade and effects of the SARS-CoV2-pandemic.

Methods

We analyzed fully anonymized data from the German Federal Statistical Office of patients with AMI between 2010 and 2020. Besides descriptive analyses of age, gender, in-hospital mortality, comorbidity burden and treatment regimen, multivariable logistic regression analyses were performed to identify independent variables associated with in-hospital mortality and different treatment.

Results

A total of 278,121 hospitalizations (120,667 male [43.4%], mean age 72.1 years) with AMI were included in this study. The total number of hospitalizations increased from 2010 (n = 24,172) to 2019 (n = 26,684) (relative increase 10.4%). In-hospital mortality decreased over the past decade from 36.6% to 2010 to 31.1% in 2019 (rel. decrease 15.2%). Independent risk factors for in-hospital mortality were older age (OR = 1.03 per year), higher comorbidity burden (OR = 1.06 per point in van Walraven score [vWs]), male gender (OR = 1.07), AMI as a secondary diagnosis (OR = 1.44), and the need for surgical (visceral surgery: OR = 1.38, vascular surgery: OR = 3.33) and endovascular treatment (OR = 1.21). We report a decline in hospitalizations during the first wave of infection in spring 2020 (rel. decrease 9.7%).

Conclusion

In-hospital mortality rate has declined over the past decade, but remains high at above 30%. Older age, increased comorbidity and male gender are independent factors for in-hospital mortality. Hospitalizations requiring vascular surgery are associated with high in-hospital mortality, followed by visceral surgery and endovascular approaches. The first wave of the SARS-CoV2-pandemic in spring 2020 implied a decrease in hospital admissions.
Comorbidity and drug resistance of smear-positive pulmonary tuberculosis patients in the yi autonomous prefecture of China: a cross-sectional study
Authors: Wang Tao , Zhou Chaoxin , Shang Lan , Zhou Xiyuan
Published: September 2023

Background

Tuberculosis (TB) has a high morbidity and mortality rate, and its prevention and treatment focus is on impoverished areas. The Liangshan Yi Autonomous Prefecture is a typical impoverished area in western China with insufficient medical resources and high HIV positivity. However, there have been few reports of TB and drug resistance in this area.

Methods

We collected the demographic and clinical data of inpatients with sputum smear positive TB between 2015 and 2021 in an infectious disease hospital in the Liangshan Yi Autonomous Prefecture. Descriptive analyses were used for the epidemiological data. The chi-square test was used to compare categorical variables between the drug-resistant and drug-susceptible groups, and binary logistic regression was used to analyse meaningful variables.

Results

We included 2263 patients, 79.9% of whom were Yi patients. The proportions of HIV (14.4%) and smoking (37.3%) were higher than previously reported. The incidence of extrapulmonary TB (28.5%) was high, and the infection site was different from that reported previously. When drug resistance gene detection was introduced, the proportion of drug-resistant patients became 10.9%. Patients aged 15–44 years (OR 1.817; 95% CI 1.162–2.840; P < 0.01) and 45–59 years (OR 2.175; 95% CI 1.335–3.543; P < 0.01) had significantly higher incidences of drug resistance than children and the elderly. Patients with a cough of ≥ 2 weeks had a significantly higher chance of drug resistance than those with < 2 weeks or no cough symptoms (OR 2.069; 95% CI 1.234–3.469; P < 0.01). Alcoholism (OR 1.741; 95% CI 1.107–2.736; P < 0.05) and high bacterial counts on sputum acid-fast smears (OR 1.846; 95% CI 1.115–3.058; P < 0.05) were significant in the univariate analysis.

Conclusions

Sputum smear-positive TB predominated in Yi men (15–44 years) with high smoking, alcoholism, and HIV rates. Extrapulmonary TB, especially abdominal TB, prevailed. Recent drug resistance testing revealed higher rates in 15–59 age group and ≥ 2 weeks cough duration. Alcohol abuse and high sputum AFB counts correlated with drug resistance. Strengthen screening and supervision to curb TB transmission and drug-resistant cases in the region.
Multicenter, randomized controlled, open label evaluation of the efficacy and safety of arbidol hydrochloride tablets in the treatment of influenza-like cases
Authors: Bai Xinfeng , Xi Suya , Chen Guiyan , Fan Xiaoying , Wang Kaiwei , Li Yong , Zhao Yang , Wang Weizhan , Tian Yingping
Published: September 2023

Objective

To study the efficacy and safety of arbidol hydrochloride tablets as a treatment for influenza-like diseases.

Methods

In this multicenter, randomized, controlled, open label study, a total of 412 influenza-like cases were collected from 14 hospitals in seven regions of Hebei Province from September 2021 to March 2022. Patients were randomly divided into two groups. The control group (n = 207) were administered oseltamivir phosphate capsules for five days and the experimental group (n = 205) were administered arbidol hydrochloride tablets for five days. The primary endpoint was the time to normal body temperature, and the secondary endpoints included the time to remission of influenza symptoms, incidence of influenza-like complications, and incidence of adverse reactions.

Results

Before treatment, there was no significant difference between the two groups in general conditions, blood routine, body temperature, or symptom severity. After treatment, there was no significant difference between the groups in the mean time to fever remission (59.24 h ± 25.21 vs. 61.05 h ± 29.47) or the mean time to remission of influenza symptoms (57.31 h ± 30.19 vs. 62.02 h ± 32.08). Survival analyses using Log-rank and Wilcoxon bilateral tests showed that there was no significant difference in fever relief time or influenza symptom relief time between the two groups. Regarding the incidence of complications and adverse events, there was only one case of tracheitis, one case of nausea, one case of vomiting, and one case of dizziness in the control group. In the experimental group, there was one case of nausea, one case of vomiting, and one case of drowsiness. In addition, one patient in the control group was hospitalized for urinary calculi.

Conclusion

There was no significant difference between the patients with influenza-like cases treated with arbidol hydrochloride tablets and those treated with oseltamivir phosphate capsules. Further, the patients treated with arbidol hydrochloride tablets had fewer adverse reactions, and thus, the tablets were safe to use.
The relationship between perineal trauma and postpartum psychological outcomes: a secondary analysis of a population-based survey
Authors: Opondo Charles , Harrison Siân , Sanders Julia , Quigley Maria A. , Alderdice Fiona
Published: September 2023

Background

Perineal trauma, involving either naturally occurring tears or episiotomy, is common during childbirth but little is known about its psychological impact. This study aimed to determine the associations between childbirth related perineal trauma and psychological outcomes reported by women three months after giving birth and to explore factors that could mediate relationships between perineal trauma and maternal psychological outcomes.

Methods

This study was a secondary analysis of data from a cross-sectional population-based survey of maternal and infant health. A total of 4,578 women responded to the survey, of which 3,307 had a vaginal birth and were eligible for inclusion into the analysis. Symptoms of depression, anxiety, and post-traumatic stress (PTS) symptoms were assessed using validated self- report measures. Physical symptoms were derived from a checklist and combined to produce a composite physical symptoms score. Regression models were fitted to explore the associations.

Results

Nearly three quarters of women experienced some degree of perineal trauma. Women who experienced perineal trauma reported having more postnatal physical symptoms (adjusted proportional odds ratio 1.47, 95%CI 1.38 to 1.57, p-value < 0.001), were more likely to report PTS symptoms (adjusted OR 1.19, 95%CI 1.04 to 1.36, p-value 0.010), and there was strong evidence that each unit increase in the physical symptoms score was associated with between 38 and 90% increased adjusted odds of adverse psychological symptoms. There was no evidence of association between perineal trauma and satisfaction with postnatal care, although there was strong evidence that satisfaction with labour and birth was associated with 16% reduced adjusted odds of depression and 30% reduced adjusted odds of PTS symptoms.

Conclusions

Women who experienced perineal trauma were more likely to experience physical symptoms, and the more physical symptoms a woman experienced the more likely she was to report having postnatal depression, anxiety and PTS symptoms. There was some evidence of a direct association between perineal trauma and PTS symptoms but no evidence of a direct association between perineal trauma and depression or anxiety. Assessment and management of physical symptoms in the postnatal period may play an important role in reducing both physical and psychological postnatal morbidity.
Using the COM-B framework to elucidate facilitators and barriers to COVID-19 vaccine uptake in pregnant women: a qualitative study
Authors: Patterson Lynsey , Berry Emma , Parsons Carole , Clarke Bronagh , Little Alison , Beggs Jillian , Chuter Antony , Jackson Tracy , Hsia Yingfen , McGrath Hannah , Millman Catherine , Murphy Siobhan , Bradley Declan T. , Milligan Sarah
Published: September 2023

Since April 2021, COVID-19 vaccines have been recommended for pregnant women. Despite this, COVID-19 vaccine uptake in this group is low compared to the non-pregnant population of childbearing age. Our aim was to understand barriers and facilitators to COVID-19 vaccine uptake among pregnant women in Northern Ireland using the COM-B framework, and so to make recommendations for public health interventions. The COM-B proposes that human behaviour is influenced by the extent to which a person has the capability, opportunity, and motivation to enact that behaviour. Understanding the factors underpinning behaviour through this lens helps discern what needs to change to change behaviour, therefore supporting the development of targeted interventions.

This study consisted of eight semi-structured interviews with new/expectant mothers who did not receive a COVID-19 vaccine dose while pregnant since April 2021, and a focus group with five participants who received at least one COVID-19 vaccine dose while pregnant. Interview and focus group data were analysed using semi-deductive reflexive thematic analysis framed by a subtle realist approach. The COM-B was used to categorise codes and subthemes were developed within each COM-B construct.

Within Psychological Capability, subthemes captured the need for consistent and reliable COVID-19 vaccine information and access to balanced and jargon-free, risk–benefit information that is tailored to the pregnant individual. The behaviour/opinions of family, friends, and local healthcare providers had a powerful influence on COVID-19 vaccine decisions (Social Opportunity). Integrating the COVID-19 vaccine as part of routine antenatal pathways was believed to support access and sense of familiarity (Physical Opportunity). Participants valued health autonomy, however experienced internal conflict driven by concerns about long-term side effects for their baby (Reflective Motivation). Feelings of fear, lack of empathy from healthcare providers, and anticipated guilt commonly underpinned indecision as to whether to get the vaccine (Automatic Motivation).

Our study highlighted that the choice to accept a vaccine during pregnancy generates internal conflict and worry. Several participants cited their concern was primarily around the safety for their baby. Healthcare professionals (HCPs) play a significant part when it comes to decision making about COVID-19 vaccines among pregnant women. HCPs and pregnant women should be involved in the development of interventions to improve the delivery and communication of information.
Reduced expression of phosphorylated ataxia-telangiectasia mutated gene is related to poor prognosis and gemcitabine chemoresistance in pancreatic cancer
Authors: Xun Jingyu , Ohtsuka Hideo , Hirose Katsuya , Douchi Daisuke , Nakayama Shun , Ishida Masaharu , Miura Takayuki , Ariake Kyohei , Mizuma Masamichi , Nakagawa Kei , Morikawa Takanori , Furukawa Toru , Unno Michiaki
Published: September 2023

Background

Loss of expression of the gene ataxia-telangiectasia mutated (ATM), occurring in patients with multiple primary malignancies, including pancreatic cancer, is associated with poor prognosis. In this study, we investigated the detailed molecular mechanism through which ATM expression affects the prognosis of patients with pancreatic cancer.

Methods

The levels of expression of ATM and phosphorylated ATM in patients with pancreatic cancer who had undergone surgical resection were analyzed using immunohistochemistry staining. RNA sequencing was performed on ATM-knockdown pancreatic-cancer cells to elucidate the mechanism underlying the invlovement of ATM in pancreatic cancer.

Results

Immunohistochemical analysis showed that 15.3% and 27.8% of clinical samples had low levels of ATM and phosphorylated ATM, respectively. Low expression of phosphorylated ATM substantially reduced overall and disease-free survival in patients with pancreatic cancer. In the pancreatic cancer cell lines with ATM low expression, resistance to gemcitabine was demonstrated. The RNA sequence demonstrated that ATM knockdown induced the expression of MET and NTN1. In ATM knockdown cells, it was also revealed that the protein expression levels of HIF-1α and antiapoptotic BCL-2/BAD were upregulated.

Conclusions

These findings demonstrate that loss of ATM expression increases tumor development, suppresses apoptosis, and reduces gemcitabine sensitivity. Additionally, loss of phosphorylated ATM is associated with a poor prognosis in patients with pancreatic cancer. Thus, phosphorylated ATM could be a possible target for pancreatic cancer treatment as well as a molecular marker to track patient prognosis.
Regulatory T cell frequency in peripheral blood of women with advanced cervical Cancer including women living with HIV
Authors: Chetty-Sebastian Devamani , Assounga Alain G.
Published: September 2023

Background

Persistent high-risk Human papillomavirus (HR-HPV) infections are the main cause of cervical cancer. Cumulative evidence implicates regulatory T cells (Tregs) as a critical factor in the failure to eliminate HPV-induced cancers leading to their persistence and progression to cancer. Also, the WHO recognised cervical cancer as 100% attributable to persistent HR-HPV infection. The province of KwaZulu-Natal (KZN) in South Africa has a high prevalence of cervical cancer and HIV infection.

Materials and methods

We evaluated Treg frequency in dual infection of HR HPV and HIV coinfection using phenotypic markers, CD4, CD25 and intracellular Foxp3, in the peripheral blood of 51 cervical cancer and 46 non-cervical cancer participants and evaluated the effect of HIV on regulatory T cell proportion. Peripheral blood mononuclear cells were surface stained with a cocktail fluorescent labelled CD4 and CD25 and subsequently with APC anti-human FoxP3 (eBioscience). Flow cytometry was performed with FACS analysis. Statistical analysis of results was done using Instat 3 program (GraphpadR). Tregs results were expressed as median ± interquartile range (IQR). Associations of cervical cancer with demographic, clinical and laboratory variables were evaluated by univariate and multivariate logistic regression analysis using SPSS version 27 (IBM).

Results

Tregs frequency was significantly higher in individuals with cervical cancer (11.00 ± 19.79%) compared to controls (1.71 ± 8.91%) (p < 0.0001). HIV infection was associated with an increase in Tregs frequency. In controls a significant difference in Tregs frequency was noted between women living with HIV (6.00 ± 10.57%, n = 9) and those without HIV (1.30 ± 6.10%, n = 37), p = 0.0023. In multivariate logistic regression, Tregs frequency was significantly associated with cervical cancer after controlling for age, smoking, weight loss, presence of STI, HIV and HPV genotype.

Discussion/Conclusion

Higher Tregs frequency was significantly associated with cervical cancer highlighting the immunosuppressive role of Tregs in cervical cancer. Treg frequency was more strongly associated with cervical cancer than HIV infection. We provide baseline data for monitoring Treg frequencies in response to new preventive and therapeutic strategies in the management of cervical cancer.
The CA125 level postoperative change rule and its prognostic significance in patients with resectable pancreatic cancer
Authors: Luo Xin , Lin Xianchao , Lin Ronggui , Yang Yuanyuan , Wang Congfei , Fang Haizong , Huang Heguang , Lu Fengchun
Published: September 2023

Background

The relationship between postoperative CA125 level changes and early recurrence after curative resection of resectable PDAC is still unclear.

Methods

The electronic medical records and follow-up data of patients with resectable pancreatic cancer were evaluated. Dynamic CA125 detection was used to identify the rules for postoperative CA125 level change and its prognostic value in patients with resectable pancreatic cancer.

Results

The study included a total of 118 patients with resectable pancreatic cancer who underwent curative resection. Early postoperative CA125 levels were significantly higher than those before surgery (P < 0.05). It decreased gradually in the group without early recurrence (P < 0.05) but not in the early recurrence group (P>0.05). There was no correlation between early postoperative CA125 levels and early recurrence (P > 0.05). CA125 levels three months after surgery were associated with an increased risk of early recurrence (P = 0.038, 95% CI (1.001–1.025)). The cutoff CA125 level at 3 months after surgery for predicting early recurrence was 22.035. Patients with CA125 levels < 22.035 three months postoperatively had similar DFS and OS, regardless of whether the value was exceeded in the early postoperative period, but these values were significantly better than those of patients with CA125 levels > 22.035 at 3 months postoperatively (p < 0.05).

Conclusions

Patients with different prognoses have different patterns of CA125 level changes. Elevations in CA125 levels > 3 months postoperatively, rather than early postoperative elevation, were associated with a poor prognosis.
Osteoblastic bone reaction in non-small cell lung cancer harboring epidermal growth factor receptor mutation treated with osimertinib
Authors: Kanaoka Kensuke , Sumikawa Hiromitsu , Oyamada Shunsuke , Tamiya Akihiro , Inagaki Yuji , Taniguchi Yoshihiko , Nakao Keiko , Matsuda Yoshinobu , Okishio Kyoichi
Published: September 2023

Background

Osteoblastic bone reaction (OBR) refers to an increase in bone density at the site of bone metastasis or the appearance of new sclerotic bone lesions after anticancer treatment. OBR can be misunderstood as disease progression. In this study, we aimed to investigate the prevalence and details of OBR and its association with clinical outcomes in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with osimertinib.

Methods

This was a single-center, retrospective cohort study. We reviewed patients who were diagnosed with EGFR-mutant NSCLC with bone metastasis and received osimertinib as a first-line treatment between February 2018 and October 2022. The OBR was evaluated by comparing baseline computed tomography (CT) scans with the first CT scan after treatment initiation.

Results

A total of 45 patients were included in this study. Thirty-seven patients (82%) developed OBR. OBR developed in 94% (n = 16) of patients with sclerotic bone lesions (n = 17) at baseline. Similarly, OBR developed in lytic and mixed bone lesions in 76% and 82% of patients with lytic and mixed lesions, respectively. Progression-free survival (PFS) did not differ significantly between patients with (OBR group) and without OBR (non-OBR group) (median PFS, 24 months vs. 17 months; hazard ratio (HR), 0.62; 95% CI, 0.24–1.6; p = 0.31). In univariate analysis, the OBR group showed a trend toward longer skeletal-related events-free survival (SRE-FS) than the non-OBR group (median SRE-FS, 26 months vs. 12 months; HR, 0.53; 95% CI, 0.21–1.33; p = 0.16). Multivariate analysis showed OBR was a significant independent predictor of SRE-FS (HR, 0.35; 95% CI, 0.13–0.92; p = 0.034).

Conclusions

OBR developed in most patients with NSCLC and bone metastasis who received osimertinib treatment. The increased incidence of OBR in patients with EGFR-mutant NSCLC with bone metastasis treated with osimertinib should not be confused with disease progression, and treatment decisions should be made carefully.
Maresin-1 inhibits high glucose induced ferroptosis in ARPE-19 cells by activating the Nrf2/HO-1/GPX4 pathway
Authors: Li Yufei , Liu Jieyu , Ma Xibo , Bai Xue
Published: September 2023

Background

Maresin-1 plays an important role in diabetic illnesses and ferroptosis is associated with pathogenic processes of diabetic retinopathy (DR). The goal of this study is to explore the influence of maresin-1 on ferroptosis and its molecular mechanism in DR.

Methods

ARPE-19 cells were exposed to high glucose (HG) condition for developing a cellular model of DR. The CCK-8 assay and flow cytometry were used to assess ARPE-19 cell proliferation and apoptosis, respectively. Furthermore, the GSH content, MDA content, ROS level, and Fe2+ level were measured by using a colorimetric GSH test kit, a Lipid Peroxidation MDA Assay Kit, a DCFH-DA assay and the phirozine technique, respectively. Immunofluorescence labelling was used to detect protein levels of ACSL4 and PTGS2. Messenger RNA and protein expression of HO-1, GPX4 and Nrf2 was evaluated through western blotting and quantitative real time-polymerase chain reaction (qRT-PCR). To establish a diabetic mouse model, mice were intraperitoneally injected 150 mg/kg streptozotocin. The MDA content, ROS level and the iron level were detected by using corresponding commercial kits.

Results

Maresin-1 promoted cell proliferation while reducing the apoptotic process in HG-induced ARPE-19 cells. Maresin-1 significantly reduced ferroptosis induced by HG in ARPE-19 cells, as demonstrated as a result of decreased MDA content, ROS level, Fe2+ level, PTGS2 expression, ACSL4 expression and increased GSH content. With respect to mechanisms, maresin-1 treatment up-regulated the mRNA expression and protein expression of HO-1, GPX4 and Nrf2 in HG-induced ARPE-19 cells. Nrf2 inhibitor reversed the inhibitory effects of maresin-1 on ferroptosis in HG-induced ARPE-19 cells. In vivo experiments, we found that Maresin-1 evidently repressed ferroptosis a mouse model of DR, as evidenced by the decreased MDA content, ROS level and iron level in retinal tissues of mice.

Conclusion

Maresin-1 protects ARPE cells from HG-induced ferroptosis via activating the Nrf2/HO-1/GPX4 pathway, suggesting that maresin-1 prevents DR development.
Joint factor analysis and approximate equipercentile linking of common trait health anxiety measures: a cross-sectional study of the 14-, 18- and 64-item health anxiety inventory, the illness attitude scale, and the 14-item Whiteley Index
Authors: Axelsson Erland , Österman Susanna , Hedman-Lagerlöf Erik
Published: September 2023

Background

Research on health anxiety has bloomed in recent years, but summaries of the literature are complicated by the use of dissimilar self-report questionnaires. Furthermore, these instruments have rarely been administered in parallel, and especially not in clinical samples. In this study, we aimed to investigate the relationship between five widespread health anxiety measures, and to draft guidelines for the conversion of different sum scores.

Methods

Clinical trial participants with principal pathological health anxiety (n = 335) and a sample of healthy volunteers (n = 88) completed the 14-item Whiteley Index (WI-14), the Illness Attitude Scale (IAS), and the 14-, 18-, and 64-item Health Anxiety Inventory (the HAI-64, HAI-18, and HAI-14). Cross-sectional data from all participants were pooled (N = 423) and we conducted a joint factor analysis and approximate equipercentile linking of the WI-14, IAS, HAI-64, HAI-18, and HAI-14.

Results

Inter-scale correlations were high (rs ≥ 0.90 and ≥ 0.88 in adjusted analyses), and the scree plot of the joint factor analysis spoke for a unifactorial solution where 89/105 items (85%) had loadings ≥ 0.40. Most items at the core of this broad trait health anxiety factor pertained to the worry about health, the fear of having or developing a serious disease, and to some extent bodily preoccupation. We present a cross-walk table of observed equipercentile linked sum scores.

Conclusions

This study speaks clearly in favor of the WI-14, IAS, HAI-64, HAI-18, and HAI-14 all tapping into the same trait health anxiety construct, the core of which appears to concern the worry about health, the fear of having or developing a serious disease, and to some extent bodily preoccupation. Based on recently reported cut-offs for the HAI-14, a reasonable cutoff for pathological health anxiety in a psychiatric setting probably lies around 7–8 on the WI-14, 52–53 on the IAS, 82–83 on the HAI-64, and 26–27 on the HAI-18.

Trial registration

ClinicalTrials.gov NCT01966705, NCT02314065.
What a critical public health perspective can add to the analysis of healthcare responses to gender-based violence that focus on asking
Authors: Goicolea Isabel
Published: September 2023

In this comment I analyze the effects of approaching gender-based violence as a public health problem, that the health system should address through ‘daring to ask’. I acknowledge the potential of the ‘daring to ask’ strategy, but I also argue that asking has effects, and that we should be aware of them.
Integrating participant feedback and concerns to improve community and individual level chemical exposure assessment reports
Authors: Samon Samantha M. , Barton Michael , Anderson Kim , Oluyomi Abiodun , Bondy Melissa , Armstrong Georgina , Rohlman Diana
Published: September 2023

Background

As exposure assessment has shifted towards community-engaged research there has been an increasing trend towards reporting results to participants. Reports aim to increase environmental health literacy, but this can be challenging due to the many unknowns regarding chemical exposure and human health effects. This includes when reports encompass a wide-range of chemicals, limited reference or health standards exist for those chemicals, and/or incompatibility of data generated from exposure assessment tools with published reference values (e.g., comparing a wristband concentration to an oral reference dose).

Methods

Houston Hurricane Harvey Health (Houston-3H) participants wore silicone wristbands that were analyzed for 1,530 organic compounds at two time-points surrounding Hurricane Harvey. Three focus groups were conducted in separate neighborhoods in the Houston metropolitan area to evaluate response to prototype community and individual level report-backs. Participants (n = 31) evaluated prototype drafts using Likert scales and discussion prompts. Focus groups were audio-recorded, and transcripts were analyzed using a qualitative data analysis program for common themes, and quantitative data (ranking, Likert scales) were statistically analyzed.

Results

Four main themes emerged from analysis of the transcripts: (1) views on the report layout; (2) expression of concern over how chemicals might impact their individual or community health; (3) participants emotional response towards the researchers; and (4) participants ability to comprehend and evaluate environmental health information. Evaluation of the report and key concerns differed across the three focus groups. However, there was agreement amongst the focus groups about the desire to obtain personal exposure results despite the uncertainty of what the participant results meant.

Conclusions

The report-back of research results (RBRR) for community and individual level exposure assessment data should keep the following key principles in mind: materials should be accessible (language level, data visualization options, graph literacy), identify known information vs unknown (e.g., provide context for what exposure assessment data means, acknowledge lack of current health standards or guidelines), recognize and respect community knowledge and history, and set participant expectations for what they can expect from the report.
Development and validation of the Post-Pandemic Fear of Viral Disease scale and its relationship with general anxiety disorder: a cross-sectional survey from Pakistan
Authors: Mahmood Qaisar Khalid , Jalil Aisha , Farooq Muhammad , Akbar Muhammad Siddique , Fischer Florian
Published: September 2023

Background

Given the worldwide reach of COVID-19, media coverage has amplified the psychological and social effects of this pandemic causing a widespread fear. Despite substantial research on the short-term psychological impact of COVID-19, its long-term consequences on mental health remain relatively unexplored. This research aims to develop and validate a Post-Pandemic Fear of Viral Disease (PPFVD) scale and to see its relationship with general anxiety disorder among the Pakistani population.

Methods

A cross-sectional online-based survey was conducted with 457 respondents in August and September 2022. We adopted the modified fear of coronavirus scale (FCV-19 S) consisting of seven items and the Generalized Anxiety Disorder (GAD) questionnaire to measure anxiety disorder. Confirmatory factor analysis was applied using the maximum likelihood estimation method. Scale dimensions and item reliability were tested for their validity and goodness of fit. SPSS and AMOS were used for data management and analyses.

Results

All inter-item correlations were found to be significant and ranged between 0.30 and 0.70. The value of Cronbach’s alpha was 0.887, indicating good reliability. Corrected item-total correlations ranged between 0.632 and 0.754. Factor loadings ranged from 0.664 to 0.810, indicating a good internal consistency. Overall, these results clearly demonstrate that the one-factor solution model for PPFVD presents a good fit to the data. The composite reliability (CR = 0.747) was also good.

Conclusions

The COVID-19 pandemic has negatively affected the mental health of people globally. This measurement scale can be trusted and used to test the PPFVD in the post-pandemic situation. Prospective research might validate this instrument in newly emerging scenarios and test it with diverse ethnic groups.