bluuebunny/crossref_metadata_2025 huggingface dataset:
EsophaCap Sponge Cytology Screening for Esophageal Squamous Cell Dysplasia and Carcinoma is Feasible in a High-Risk Area in Western India
Authors: Bhatt Maunil , Sridhar Praveen , Asokan Sainath , Shah Parth , Gandhi Fenil , Shah Pratiksha , Patel Parth , Suzuki Kei , Rajput Sanjay , Parmar Vipal , Mehta Bhavna , Godfrey Tony E. , Litle Virginia R.
Published: March 2024

Objective:

Conventional endoscopy remains the gold standard for detecting esophageal squamous cell carcinoma (ESCC) despite its high cost and need for expertise. In resource-poor regions, a less labor-intensive yet accurate screening tool is needed. The purpose of this study is to assess feasibility of establishing a non-endoscopic screening program in rural India and to test the diagnostic accuracy of the EsophaCap swallowable sponge in detecting ESCC in a high-risk patient population.

Methods:

A prospective cohort study was conducted between 2017 and 2019, in which subjects with risk factors for ESCC (tobacco smoking or chewing, betel nut/leaf, alcohol and hot beverage consumption) were approached during upper endoscopy visits at a clinic in Western India. After obtaining EsophaCap sponge cytology samples, random endoscopic biopsies were obtained at 20 and 30 cm from the incisors. Histologic diagnoses were confirmed and select biopsy samples were sequenced for genomic aberrations. Visual Analog Scale (VAS) scores were used to assess patient experience of sponge swallowing (range 1-5, “very comfortable” to “very uncomfortable”).

Results:

In our cohort of 178 patients, 157 (88%) were males. Mean age was 52 ± 12 years. Sixty-eight (38%) patients were current cigarette or bidi smokers; 132 (74%) patients were daily tobacco chewers, and 83 (47%) patients chewed betel nuts/leaves on a daily basis. Forty-six (26%) patients were daily alcohol users and 151 (85%) patients drank ≥3 hot beverages per day. The median number of risk factors per patient was 3. The first-time swallow rate of the encapsulated sponge was successful in 190/200 (95%) patients. Median VAS score was 2 (“comfortable”). EsophaCap cytology revealed 6 (3%) patients with atypical squamous cells of unknown significance (ASCUS) and 3 (1%) patients with dysplasia. Based on the endoscopic biopsies, 6 (3%) patients had ESCC, 4 (2%) patients had lesions with squamous dysplasia, and 63 (35%) patients had esophageal leukoplakia. Four patients classified as ASCUS pathology via EsophaCap were normal, benign, or leukoplakia via endoscopy. EsophaCap’s sensitivity and specificity for detecting dysplasia or ESCC by histology was 30% and 97%, respectively.

Conclusions:

Establishing a non-endoscopic screening program in a high-risk area with language barriers and low medical literacy is very safe and feasible. EsophaCap may help identify ASCUS patients in need of serial endoscopic monitoring. Further studies of combined sponge cytology with immunohistochemistry studies are necessary to improve accuracy of ESCC screening.
A Balancing Act of Leadership: The Practice of Shaping the Direction of a Project Portfolio
Authors: Kortantamer Dicle
Published: March 2024

This article explores the practice of shaping the project portfolio direction through the lens of leadership. Focusing on a public setting, it uncovers three interrelated activities: developing ownership, networking, and de-personalizing. These activities can be accomplished through continuous balancing of substantive–symbolic and visible–subtle acts, institutional structures and their improvisations, and hierarchical and distributed leadership. The article contributes to (1) the project portfolio management literature by offering the concept of hybrid leadership and insights into the alignment of diverse stakeholder interests and worldviews, and (2) to the leadership literature by critiquing the leadership-as-practice movement and advancing explanations of the interplay between hierarchical and distributed leadership.
Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial
Authors: Kenet Gili , Nolan Beatrice , Zulfikar Bulent , Antmen Bulent , Kampmann Peter , Matsushita Tadashi , You Chur-Woo , Vilchevska Kateryna , Bagot Catherine N. , Sharif Azizan , Peyvandi Flora , Young Guy , Negrier Claude , Chi Jiarui , Kittner Barbara , Sussebach Christian , Shammas Fadi , Mei Baisong , Andersson Shauna , Kavakli Kaan
Published: March 2024

Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This phase 3, open-label study evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis. Participants continued their prior BPA/CFC prophylaxis for 6 months before switching to once-monthly 80 mg fitusiran prophylaxis for 7 months (onset and efficacy periods). Primary end point was annualized bleeding rate (ABR) in the BPA/CFC prophylaxis and fitusiran efficacy period. Secondary end points included spontaneous ABR (AsBR) and joint ABR (AjBR). Safety and tolerability were assessed. Of 80 enrolled participants, 65 (inhibitor, n = 19; noninhibitor, n = 46) were eligible for ABR analyses. Observed median ABRs were 6.5 (interquartile range [IQR], 2.2-19.6)/4.4 (IQR, 2.2-8.7) with BPA/CFC prophylaxis vs 0.0 (IQR, 0.0-0.0)/0.0 (IQR, 0.0-2.7) in the corresponding fitusiran efficacy period. Estimated mean ABRs were substantially reduced with fitusiran by 79.7% (P = .0021) and 46.4% (P = .0598) vs BPA/CFC prophylaxis, respectively. Forty-one participants (63.1%) experienced 0 treated bleeds with fitusiran vs 11 (16.9%) with BPAs/CFCs. Median AsBR and AjBR were both 2.2 with BPA/CFC prophylaxis and 0.0 in the fitusiran efficacy period. Two participants (3.0%) experienced suspected or confirmed thromboembolic events with fitusiran. Once-monthly fitusiran prophylaxis significantly reduced bleeding events vs BPA/CFC prophylaxis in PwHA/B, with or without inhibitors, and reported adverse events were generally consistent with previously identified risks of fitusiran. This trial was registered at www.ClinicalTrials.gov as #NCT03549871.
Vector integration and fate in the hemophilia dog liver multiple years after AAV-FVIII gene transfer
Authors: Batty Paul , Fong Sylvia , Franco Matteo , Sihn Choong-Ryoul , Swystun Laura L. , Afzal Saira , Harpell Lorianne , Hurlbut David , Pender Abbey , Su Cheng , Thomsen Hauke , Wilson Christopher , Youssar Loubna , Winterborn Andrew , Gil-Farina Irene , Lillicrap David
Published: March 2024

Gene therapy using adeno-associated virus (AAV) vectors is a promising approach for the treatment of monogenic disorders. Long-term multiyear transgene expression has been demonstrated in animal models and clinical studies. Nevertheless, uncertainties remain concerning the nature of AAV vector persistence and whether there is a potential for genotoxicity. Here, we describe the mechanisms of AAV vector persistence in the liver of a severe hemophilia A dog model (male = 4, hemizygous; and female = 4, homozygous), more than a decade after portal vein delivery. The predominant vector form was nonintegrated episomal structures with levels correlating with long-term transgene expression. Random integration was seen in all samples (median frequency, 9.3e−4 sites per cell), with small numbers of nonrandom common integration sites associated with open chromatin. No full-length integrated vectors were found, supporting predominant episomal vector-mediated long-term transgene expression. Despite integration, this was not associated with oncogene upregulation or histopathological evidence of tumorigenesis. These findings support the long-term safety of this therapeutic modality.
Nilotinib with or without cytarabine for Philadelphia-positive acute lymphoblastic leukemia
Authors: Chalandon Yves , Rousselot Philippe , Chevret Sylvie , Cayuela Jean-Michel , Kim Rathana , Huguet Françoise , Chevallier Patrice , Graux Carlos , Thiebaut-Bertrand Anne , Chantepie Sylvain , Thomas Xavier , Vincent Laure , Berthon Céline , Hicheri Yosr , Raffoux Emmanuel , Escoffre-Barbe Martine , Plantier Isabelle , Joris Magalie , Turlure Pascal , Pasquier Florence , Belhabri Amine , Guepin Gabrielle Roth , Blum Sabine , Gregor Michael , Lafage-Pochitaloff Marina , Quessada Julie , Lhéritier Véronique , Clappier Emmanuelle , Boissel Nicolas , Dombret Hervé
Published: March 2024

We previously demonstrated that a reduced-intensity chemotherapy schedule can safely replace hyper-CVAD (cyclophosphamide-vincristine-doxorubicin [Adriamycin]-dexamethasone) cycle 1 when combined with imatinib in adults with Philadelphia-positive acute lymphoblastic leukemia. In the present randomized GRAAPH-2014 trial, we used nilotinib and addressed the omission of cytarabine (Ara-C) in consolidation. The primary objective was the major molecular response (MMR) rate measured by BCR::ABL1 quantification after cycle 4 (end of consolidation). All patients were eligible for allogeneic stem cell transplant (SCT), whereas those in MMR could receive autologous SCT, followed by 2-year imatinib maintenance in both cases. After the enrollment of 156 of 265 planed patients, the data and safety monitoring board decided to hold the randomization because of an excess of relapse in the investigational arm. Among the 155 evaluable patients, 76 received Ara-C during consolidation (arm A) and 79 did not (arm B). Overall, 133 patients (85%) underwent SCT, 93 allogeneic and 40 autologous. The noninferiority end point regarding MMR was reached with 71.1% (arm A) and 77.2% (arm B) of patients reaching MMR. However, the 4-year cumulative incidence of relapse was higher in arm B compared with arm A (31.3% [95% confidence interval {CI}, 21.1%-41.9%] vs 13.2% [95% CI, 6.7%-21.9%]; P = .017), which translated to a lower relapse-free survival. With a median follow-up of 3.8 years, 4-year overall survival was 79.0% (95% CI, 70.6%-89.3%) in arm A vs 73.4% (95% CI, 63.9%-84.4%) in arm B (P = .35). Despite a noninferior rate of MMR, more relapses were observed when ARA-C was omitted without impact on survival. ClinicalTrials.gov ID, NCT02611492.
Cardiopulmonary exercise testing and body composition
Authors: Karlsson Per , Lind Lars , Michaëlsson Karl , Malinovschi Andrei
Published: March 2024

Background

The cardiopulmonary exercise test (CPET) evaluates cardiopulmonary function. In light of the obesity epidemic, it is important to understand how body composition affects interpretation of CPET results. The aim of the present study was to assess the relationship between CPET measures, other than peak oxygen uptake, and body composition.

Method

A total of 330 participants, aged 50 years, performed both a CPET and dual-energy X-ray absorptiometry (DXA). From the CPET, peak exercise respiratory exchange ratio (RER), ventilatory efficiency (V̇E/V̇CO2slope) and work efficiency (ΔV̇O2/ΔWR) were recorded. Pearson's correlation was used to assess the association between CPET measures and selected body composition measures, including body mass index (BMI), waist circumference, fat mass, lean mass, body fat percentage and percentage trunk fat to fat mass. All analyses were done stratified by sex. A p-value <0.05 defined statistical significance.

Results

RER was negatively correlated with body composition measures; the strongest correlation was observed with waist circumference in females (r= −0.36).V̇E/V̇CO2slope had no significant correlations with any body composition measures. ΔV̇O2/ΔWR was positively correlated with the body composition measures; the strongest correlation was observed with BMI (r=0.24). The additive role of percentage body fat and percentage trunk fat were studied in a linear regression model using waist circumference and BMI to predict the aforementioned CPET measures and no additive role was found.

Conclusion

RER and ΔV̇O2/ΔWR may be influenced by body composition whileV̇E/V̇CO2slope is not affected. Adiposity measures from DXA add no additional explanatory value to the CPET measures.
Long-term associations of PM1versusPM2.5and PM10with asthma and asthma-related respiratory symptoms in the middle-aged and elderly population
Authors: Zheng Xue-yan , Guo Shu-jun , Hu Jian-xiong , Meng Rui-lin , Xu Yan-jun , Lv Yun-hong , Wang Ye , Xiao Ni , Li Chuan , Xu Xiao-jun , Zhao De-jian , Zhou Hong-ye , He Jia-hui , Tan Xiao-min , Wei Jing , Lin Li-feng , Guan Wei-jie
Published: March 2024

Background

Few studies have compared the associations between long-term exposures to particulate matters (aerodynamic diameter ≤1, ≤2.5 and ≤10 µm: PM1, PM2.5and PM10, respectively) and asthma and asthma-related respiratory symptoms. The objective of the present study was to compare the strength of the aforementioned associations in middle-aged and elderly adults.

Methods

We calculated the mean 722-day personal exposure estimates of PM1, PM2.5and PM10at 1 km×1 km spatial resolution between 2013 and 2019 at individual levels from China High Air Pollutants (CHAP) datasets. Using logistic regression models, we presented the associations as odds ratios and 95% confidence intervals, for each interquartile range (IQR) increase in PM1/PM2.5/PM10concentration. Asthma denoted a self-reported history of physician-diagnosed asthma or wheezing in the preceding 12 months.

Results

We included 7371 participants in COPD surveillance from Guangdong, China. Each IQR increase in PM1, PM2.5and PM10was associated with a greater odds (OR (95% CI)) of asthma (PM1: 1.22 (1.02–1.45); PM2.5: 1.24 (1.04–1.48); PM10: 1.30 (1.07–1.57)), wheeze (PM1: 1.27 (1.11–1.44); PM2.5: 1.30 (1.14–1.48); PM10: 1.34 (1.17–1.55)), persistent cough (PM1: 1.33 (1.06–1.66); PM2.5: 1.36 (1.09–1.71); PM10: 1.31 (1.02–1.68)) and dyspnoea (PM1: 2.10 (1.84–2.41); PM2.5: 2.17 (1.90–2.48); PM10: 2.29 (1.96–2.66)). Sensitivity analysis results were robust after excluding individuals with a family history of allergy. Associations of PM1, PM2.5and PM10with asthma and asthma-related respiratory symptoms were slightly stronger in males.

Conclusion

Long-term exposure to PM is associated with increased risks of asthma and asthma-related respiratory symptoms.
Genome-wide association studies highlight novel risk loci for septal defects and left-sided congenital heart defects
Authors: Broberg Martin , Ampuja Minna , Jones Samuel , Ojala Tiina , Rahkonen Otto , Kivelä Riikka , Priest James ,   FinnGen, Palotie Aarno , Ollila Hanna M. , Helle Emmi
Published: March 2024

Background

Congenital heart defects (CHD) are structural defects of the heart affecting approximately 1% of newborns. They exhibit low penetrance and non-Mendelian patterns of inheritance as varied and complex traits. While genetic factors are known to play an important role in the development of CHD, the specific genetics remain unknown for the majority of patients. To elucidate the underlying genetic risk, we performed a genome wide association study (GWAS) of CHDs in general and specific CHD subgroups using the FinnGen Release 10 (R10) (N > 393,000), followed by functional fine-mapping through eQTL and co-localization analyses using the GTEx database.

Results

We discovered three genome-wide significant loci associated with general CHD. Two of them were located in chromosome 17: 17q21.32 (rs2316327, intronic: LRRC37A2, Odds ratio (OR) [95% Confidence Interval (CI)] = 1.17[1.12–1.23], p = 1.5 × 10–9) and 17q25.3 (rs1293973611, nearest: BAHCC1, OR[95%CI] = 4.48[2.80–7.17], p = 7.0 × 10–10), respectively, and in addition to general CHD, the rs1293973611 locus was associated with the septal defect subtype. The third locus was in band 1p21.2 (rs35046143, nearest: PALMD, OR[95%CI] = 1.15[1.09–1.21], p = 7.1 × 10–9), and it was associated with general CHD and left-sided lesions. In the subgroup analysis, two additional loci were associated with septal defects (rs75230966 and rs6824295), and one with left-sided lesions (rs1305393195). In the eQTL analysis the variants rs2316327 (general CHD), and rs75230966 (septal defects) both located in 17q21.32 (with a LD r2 of 0.41) were both predicted to significantly associate with the expression of WNT9B in the atrial appendage tissue category. This effect was further confirmed by co-localization analysis, which also implicated WNT3 expression in the atrial appendage. A meta-analysis of general CHD together with the UK Biobank (combined N = 881,678) provided a different genome-wide significant locus in LRRC37A2; rs16941382 (OR[95%CI] = 1.15[1.11–1.20], p = 1.5 × 10–9) which is in significant LD with rs2316327.

Conclusions

Our results of general CHD and different CHD subcategories identified a complex risk locus on chromosome 17 near BAHCC1 and LRRC37A2, interacting with the genes WNT9B, WNT3 and MYL4, may constitute potential novel CHD risk associated loci, warranting future experimental tests to determine their role.
Prolonged abdominal pregnancy incidentally discovered during cesarean section: a case report
Authors: Diaouga Hamidou Soumana , Yacouba Maimouna Chaibou , Hissen Tidjani Mahamat , Oumara Maina , Bako Inoussa Daouda , Garba Rahamatou Madeleine , Idi Nafiou , Nayama Madi
Published: March 2024

Background

Abdominal pregnancy is a rare medical condition that is still missed in developing countries due to inadequate medical facilities. The clinical indicators manifest in various forms and are nonspecific, making it challenging to diagnose and often leading to delayed detection. However, obstetric ultrasound serves as an essential tool in early detection. Our objective was to share our experience dealing with this condition and emphasise the importance of early ultrasound diagnosis through efficient pregnancy monitoring in our regions.

Case presentation

35-year-old Black African woman who had ten months of amenorrhea sought consultation due to an absence of active foetal movements. Her pregnancy was of 39 weeks with fetal demise which was confirmed following clinical examination and ultrasound. She underwent cesarean section in view of transverse position of fetus. During cesarean section, the fetus was found within the abdominal cavity with the placenta attached over the left iliac fossa including surface of left ovary. The uterus and right adnexa were within normal limits. A 2600 g macerated fetus with placenta and membranes were extracted without any complications. The maternal outcome was successful.

Conclusions

Abdominal pregnancy remained an inadequately diagnosed condition in developing countries. It is imperative to increase awareness among pregnant women regarding high-quality prenatal care, including early obstetric ultrasound, from conception. Meanwhile, healthcare professionals should receive continuous training and the technical platform modernised. To ensure accurate diagnosis, the location of the gestational sac must be identified for every pregnant woman during their initial ultrasound appointment.
Association of the second birth mode of delivery and interval with maternal pelvic floor changes: a prospective cohort study
Authors: Wu Xiaoli , Zheng Xiu , Yi Xiaohong , Fan Bolin
Published: March 2024

Background

This study aimed to explore the association of the second birth delivery mode and interval with maternal pelvic floor changes.

Methods

This prospective cohort study included women who had a first delivery and were in weeks 36–41 of a subsequent pregnancy at Panzhihua Central Hospital between July 2017 and June 2018. The primary outcomes of the study were the hiatus area at 6 months postpartum and bladder neck (mm) at rest and during a maximum Valsalva maneuver.

Results

There were 112 women with vaginal delivery and 182 with Cesarean section. The hiatus area and hiatus circumference decreased at all time points (all P < 0.001). The women with Cesarean section had a smaller hiatus area and circumference (P < 0.001 and P < 0.001). The hiatus diameters decreased with time in both groups (all P < 0.001) and were smaller after Cesarean section (both P < 0.001). The bladder neck at maximum Valsalva increased with time (all P < 0.001) without significant differences between the two groups. Finally, the proportion of patients with POP-Q stage 0/I increased with time in both groups (all P < 0.001), with the proportions being higher in the Cesarean group (P = 0.002). The birth interval was negatively correlated with the hiatus area (B=-0.17, 95%CI: -0.25, -0.08, P < 0.001) and positively correlated with the bladder neck at rest (B = 0.22, 95%CI: 0.08, 0.35, P = 0.001) and at maximum Valsalva (B = 0.85, 95%CI: 0.65, 1.05, P < 0.001).

Conclusions

In conclusion, the mode of delivery at the second birth could influence the hiatus area and circumference and bladder neck size. The birth interval was negatively correlated with the hiatus area and positively correlated with the bladder neck at rest and at maximum Valsalva.
Is early bilateral compression ultrasonography and D-dimer monitoring appropriately for prophylaxis and diagnosis of deep venous thrombosis after cesarean section women: a single-center observation study of Chinese Han population
Authors: Chen Xiuying , Jiang Haiyan , Zhou Aiping , Zhang Quan , Du Minmin , Sun Yun , Zhao Baihui
Published: March 2024

Background

Venous thromboembolism (VTE) is most prevalent among parturients following a cesarean section (CS). The objective of this study was to assess the practical utility of bilateral compression ultrasonography (CUS) of the lower limbs, coupled with D-dimer monitoring, in the early diagnosis of VTE within the Han Chinese population.

Methods

Our prospective observational study included 742 women who underwent CUS and D-dimer testing on the first day post-CS. Subsequently, telephone or outpatient follow-ups were conducted until 42 days postpartum. States of hypercoagulation and thrombosis, as indicated by CUS, were classified as CUS abnormal. A D-dimer level ≥ 3 mg/l was considered the D-dimer warning value. Early ambulation and mechanical prophylaxis were universally recommended for all parturients post-CS. A sequential diagnostic strategy, based on the 2015 RCOG VTE risk-assessment tool, was employed. Therapeutic doses of low-molecular-weight heparin (LMWH) were administered for the treatment of thromboembolic disease. Prophylactic doses of LMWH were given for VTE prophylaxis in parturients with hypercoagulative status accompanied by D-dimer levels ≥ 3 mg/l. All high-risk women (RCOG score ≥ 4 points) were additionally treated with preventive LMWH. Statistical analyses were conducted using the R statistical software, with a two-sided P value < 0.05 considered statistically significant.

Results

Fifteen cases of VTE and 727 instances without VTE were observed. The overall VTE rate post-CS was 2.02% (15/742), with 66.7% (10/15) being asymptomatic. Eleven patients received a VTE diagnosis on the first postpartum day. Among the 41 parturients exhibiting hypercoagulation ultrasound findings and D-dimer levels ≥ 3 mg/l, despite receiving pharmacological VTE prophylaxis with LMWH, 4.88% (2/41) in the high-risk group were eventually diagnosed with VTE. A total of 30.86% (229/742) exhibited normal ultrasound findings and D-dimer levels < 3 mg/l on the first day post-CS, with no VTE occurrences in the postpartum follow-up. According to RCOG’s recommendation, 78.03% (579/742) of cesarean delivery women should receive prophylactic anticoagulation, while only 20.62% (153/742) met our criterion for prophylactic anticoagulation.

Conclusion

The strategy of timely routine bilateral CUS and D-dimer monitoring is conducive to the early diagnosis and treatment of VTE, significantly reducing the use of LMWH in the Chinese Han population.
Regulation of cancer stem cells by CXCL1, a chemokine whose secretion is controlled by MCM2
Authors: Kahm Yeon-Jee , Kim In-Gyu , Kim Rae-Kwon
Published: March 2024

Background

A high expression pattern of minichromosome maintenance 2 (MCM2) has been observed in various cancers. MCM2 is a protein involved in the cell cycle and plays a role in cancer growth and differentiation by binding to six members of the MCM subfamily. The MCM protein family includes MCM2 through MCM7.

Methods

MCM2 has shown high expression in both lung cancer stem cells (LCSCs) and glioma stem cells (GSCs). We investigated the characteristics of CSCs and the regulation of the epithelial-to-mesenchymal transition (EMT) phenomenon in LCSCs and GSCs by MCM2. Additionally, we explored secreted factors regulated by MCM2.

Results

There was a significant difference in survival rates between lung cancer patients and brain cancer patients based on MCM2 expression. MCM2 was found to regulate both markers and regulatory proteins in LCSCs. Moreover, MCM2 is thought to be involved in cancer metastasis by regulating cell migration and invasion, not limited to lung cancer but also identified in glioma. Among chemokines, chemokine (C-X-C motif) ligand 1 (CXCL1) was found to be regulated by MCM2.

Conclusions

MCM2 not only participates in the cell cycle but also affects cancer cell growth by regulating the external microenvironment to create a favorable environment for cells. MCM2 is highly expressed in malignant carcinomas, including CSCs, and contributes to the malignancy of various cancers. Therefore, MCM2 may represent a crucial target for cancer therapeutics.
Measurement of the distance between corneal apex and pupil center in patients following small-incision lenticule extraction or implantable collamer lens implantation and its correlation with the surgical-induced astigmatism
Authors: Qian Yishan , Ding Lan , Ding Yanlan , Jiang Lin , Liu Zesheng , Zhou Xingtao
Published: March 2024

Background

To investigate the change in the distance between corneal apex and pupil center after small-incision lenticule extraction (SMILE) or implantable collamer lens (ICL) implantation and its correlation with surgical-induced astigmatism (SIA).

Methods

This study included patients who had undergone SMILE (n = 112) or ICL implantation (n = 110) to correct myopia and myopic astigmatism. The angle kappa was measured using a Scheimpflug imaging device (Pentacam) and represented as Cartesian values between the pupil center and the corneal vertex (X, Y) and chord u ($$ \sqrt{{X}^{2}+{Y}^{2}}@ $$orientation), and was compared pre- and post-operative.

Results

Following SMILE, the magnitude of chord u$$ (\sqrt{{X}^{2}+{Y}^{2}}$$) significantly increased in both eyes (Wilcoxon signed-rank test, OD: P<0.001; OS: P=0.007), while no significant change was observed in the orientation. A significant correlation was found between the J0 component of SIA and the change in the magnitude of chord u for both eyes (OD: R2=0.128, P<0.001; OS: R2=0.033, P=0.004). After ICL implantation, the orientation of the chord u was significantly different in the right eye (Wilcoxon signed-rank test, P = 0.008), and the Y-intercept significantly decreased in both eyes (Wilcoxon signed-rank test, P<0.001). A significant correlation was found between J0 of SIA and the change in the magnitude of chord u for the right eyes (R2=0.066, P=0.002). A significant correlation was found between J45 of SIA and the change in the magnitude of chord u for the left eyes (R2=0.037, P=0.044).

Conclusions

The magnitude of the chord u increased following the SMILE procedure, whereas the Y-intercept significantly decreased after ICL implantation. SIA was related to the change in the magnitude of chord u.
Sling for the sling: a new technique for long-term correction of severe congenital ptosis
Authors: Kotb Ahmed N. , Soliman Noha M. , Raza Ahmer , Nour Noran A. , Mattout Hala K.
Published: March 2024

Introduction

Severe congenital ptosis poses a complex challenge for oculoplastic surgeons, requiring meticulous surgical intervention to restore eyelid function and improve aesthetic outcomes mainly by using frontalis sling approach. A crucial issue in frontalis sling surgeries is the sustainability of effect.

Purpose

This retrospective study reports the outcomes of two surgical techniques for treating severe congenital ptosis in the paediatric age group: Silicon rods ptosis sling and a novel technique involving the use of Silicon rods with green braided polyester (Ethibond) sutures to secure the rods in place “sling for the sling”.

Methods

The medical records of children who underwent frontalis suspension were reviewed in a retrospective fashion. We identified two groups; the first group (20 patients: 35 eyelids) had the traditional frontalis suspension surgery using silicone suspension set, the second group (14 patients: 25 eyelids) was operated using the new “sling for sling” technique. We used the postoperative marginal reflex distance-1 (MRD-1) as the primary outcome measure while the frequency of both wound related complications and recurrence were considered as secondary outcome measures. Post operative data were collected and compared after 1 month, 6 months, 12 months, and 18 months.

Results

Preliminary results indicate promising outcomes for both techniques, with significant improvement in eyelid elevation observed in both groups. However, the novel technique using Silicon rods with Ethibond sutures demonstrated enhanced sustainability, leading to a more durable outcome with significantly less recurrence.

Conclusion

This study highlights the potential benefits of the novel technique in treating severe congenital ptosis and introduces an innovative approach to Silicone rods fixation to achieve a long-term corrective effect.
Importance about use of high-throughput sequencing in pediatric: case report of a patient with Fanconi-Bickel syndrome
Authors: Abarca-Barriga Hugo Hernán , Laso-Salazar María Cristina , Orihuela-Tacuri Diego , Chirinos-Saire Jenny , Venero-Nuñez Anahí
Published: March 2024

Background

Fanconi-Bickel syndrome is characterized by hepatorenal disease caused by anomalous glycogen storage. It occurs due to variants in the SLC2A2 gene. We present a male patient of 2 years 7 months old, with failure to thrive, hepatomegaly, metabolic acidosis, hypophosphatemia, hypokalemia, hyperlactatemia.

Results

Exome sequencing identified the homozygous pathogenic variant NM_000340.2(SLC2A2):c.1093 C > T (p.Arg365Ter), related with Fanconi-Bickel syndrome. He received treatment with bicarbonate, amlodipine, sodium citrate and citric acid solution, enalapril, alendronate and zolendronate, and nutritional management with uncooked cornstarch, resulting in an improvement of one standard deviation in weight and height.

Conclusions

The importance of knowing the etiology in rare genetic disease is essential, not only to determine individual and familial recurrence risk, but also to establish the treatment and prognosis; in this sense, access to a new genomic technology in low- and middle-income countries is essential to shorten the diagnostic odyssey.
Low-intensity mindfulness and cognitive–behavioral therapy for social anxiety: a pilot randomized controlled trial
Authors: Noda Shota , Shirotsuki Kentaro , Nakao Mutsuhiro
Published: March 2024

Background

Cognitive–behavioral therapy (CBT) effectively improves the clinical symptoms of social anxiety disorder. However, there are non-responders who cannot decrease their cost/probability bias significantly; hence, their social anxiety symptoms remain unaddressed. Mindfulness training and cognitive–behavioral approaches promote a reduction in cost/probability bias and social anxiety symptoms. This study examines the effectiveness of a four-session program of mindfulness and CBT (M-CBT) in a non-clinical sample of individuals with high social anxiety.

Methods

Participants were 50 Japanese undergraduate students (37 women and 13 men) randomly allocated to an intervention group (n = 27) and a control group (n = 23). The intervention group underwent a four-session M-CBT program, while the control group did not receive any treatment.

Results

A group × time analysis of covariances showed significant interactions in the negative cognition generated when paying attention to others in probability bias, fear of negative evaluation by others, dispositional mindfulness, depressive symptoms, and subjective happiness. M-CBT also produced significant pre-post improvements in the above outcomes with moderate to high effect sizes (ds = .51–1.55). Conversely, there were no interactions in social anxiety symptoms and self-focused attention.

Conclusions

These results indicate that M-CBT was effective for the negative cognition generated when paying attention to others in probability bias, fear of negative evaluation by others, dispositional mindfulness, depressive symptoms, and subjective happiness. The combination of mindfulness training with cognitive restructuring is proposed as potentially helpful for individuals with probability bias, leading to negative cognition from paying attention to others.

Trial registration

University Hospital Medical Information Network (UMIN CTR) UMIN000036763. Registered May 16, 2019.
Is new tech a pain in the neck? The impact of introducing new technologies in home-care on neck pain: a prospective study
Authors: Christensen Jan Olav , Johannessen Håkon
Published: March 2024

Background

Home healthcare services are increasingly utilizing novel technologies to enhance quality and efficiency of caregiving, to reduce workloads and compensate for expected labor shortages in the future due to ageing populations. However, rapid, ongoing implementation of new technologies may demand considerable adaptation for employees. The objective of this study was to prospectively examine associations of newly introduced work technologies with neck pain complaints.

Methods

With a nationally representative prospective sample of home-care workers in Norway (N = 887), we estimated effects of 1) introducing new technologies and 2) the appraised quality of training during implementation on neck pain eight months after.

Results

A majority of employees reported new technologies having been introduced the previous 12 months (73.8%). This was not by itself associated with neck pain. However, perceived high quality of training was associated with less subsequent neck pain, also after adjustment for job demands and job control. The strongest effect was seen for “very good” versus “very poor” quality training (OR 0.35, 95% CI 0.17,0.71, in the fully adjusted model). Cross-lagged path analyses ruled out potential reverse causation stemming from the influence of pain on needs for or appraisals of training.

Conclusion

The present findings suggest the introduction of new work technologies has a significant impact on home-care workers’ health, depending on the quality of training during implementation. This highlights the need to include training programs in risk assessments when implementing new technologies.
Cyclin A1 (CCNA1) inhibits osteoporosis by suppressing transforming growth factor-beta (TGF-beta) pathway in osteoblasts
Authors: Du Xiao , Zang Chuanyi , Wang Qinglei
Published: March 2024

Background

Osteoporosis is a genetic disease caused by the imbalance between osteoblast-led bone formation and osteoclast-induced bone resorption. However, further gene-related pathogenesis remains to be elucidated.

Methods

The aberrant expressed genes in osteoporosis was identified by analyzing the microarray profile GSE100609. Serum samples of patients with osteoporosis and normal group were collected, and the mRNA expression of candidate genes was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The mouse cranial osteoblast MC3T3-E1 cells were treated with dexamethasone (DEX) to mimic osteoporosis in vitro. Alizarin Red staining and alkaline phosphatase (ALP) staining methods were combined to measure matrix mineralization deposition of MC3T3-E1 cells. Meanwhile, the expression of osteogenesis related genes including alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), Osterix, and bone morphogenetic protein 2 (BMP2) were evaluated by qRT-PCR and western blotting methods. Then the effects of candidate genes on regulating impede bone loss caused by ovariectomy (OVX) in mice were studied.

Results

Cyclin A1 (CCNA1) was found to be significantly upregulated in serum of osteoporosis patients and the osteoporosis model cells, which was in line with the bioinformatic analysis. The osteogenic differentiation ability of MC3T3-E1 cells was inhibited by DEX treatment, which was manifested by decreased Alizarin Red staining intensity, ALP staining intensity, and expression levels of ALP, OCN, OPN, Osterix, and BMP2. The effects of CCNA1 inhibition on regulating osteogenesis were opposite to that of DEX. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that genes negatively associated with CCNA1 were enriched in the TGF-beta signaling pathway. Inhibitor of TGF-beta signaling pathway partly reversed osteogenesis induced by suppressed CCNA1. Furthermore, suppressed CCNA1 relieved bone mass of OVX mice in vivo.

Conclusion

Downregulation of CCNA1 could activate TGF-beta signaling pathway and promote bone formation, thus playing a role in treatment of osteoporosis.
Identification of novel AKT1 inhibitors from Sapria himalayana bioactive compounds using structure-based virtual screening and molecular dynamics simulations
Authors: Ralte Laldinfeli , Sailo Hmingremhlua , Kumar Rakesh , Khiangte Laldinliana , Kumar Nachimuthu Senthil , Singh Yengkhom Tunginba
Published: March 2024

Through the experimental and computational analyses, the present study sought to elucidate the chemical composition and anticancer potential of Sapria himalayana plant extract (SHPE). An in vitro analysis of the plant extract was carried out to determine the anticancer potential. Further, network pharmacology, molecular docking, and molecular dynamic simulation were employed to evaluate the potential phytochemical compounds for cervical cancer (CC) drug formulations. The SHPE exhibited anti-cancerous potential through inhibition properties against cancer cell lines. The LC-MS profiling showed the presence of 14 compounds in SHPE. Using network pharmacology analysis, AKT1 (AKT serine/threonine kinase 1) is identified as the possible potential target, and EGFR (Epidermal Growth Factor Receptor) is identified as the possible key signal pathway. The major targets were determined to be AKT1, EGFR by topological analysis and molecular docking. An in silico interaction of phytoconstituents employing molecular docking demonstrated a high binding inclination of ergoloid mesylate and Ergosta-5,7,9(11),22-tetraen-3-ol, (3.beta.,22E)- with binding affinities of -15.5 kcal/mol, and -11.3 kcal/mol respectively. Further, MD simulation and PCA analyses showed that the phytochemicals possessed significant binding efficacy with CC protein. These results point the way for more investigation into SHPE compound’s potential as CC treatment.

Graphical Abstract
Measuring the continuing care needs of inpatients in rural China
Authors: Liu Haoran , Wang Zhifan , Hu Juan , Xu Qiushuang , Yang Lei , Jian Weiyan
Published: March 2024

Background

International experience shows that the suitability of a high-performance healthcare system for its given purposes is reflected in its ability to provide a continuum of services that match the changing health status of the given population. Although many low- and middle-income countries have sought to bring movement away from hospital-centered and towards patient-centered healthcare, such efforts have often had poor results, and one of the major reasons for this is the inability to accurately identify which inpatients need continuing care and what kind of continuing of care is needed.

Objectives

To measure and assess the continuing care needs of discharged patients and its influencing factors in rural China.

Methods

Data were obtained from the hospital database of Medical Center M in County Z from May to July 2022. County Z is a county of 1 million people in central China. The database includes basic patient information, disease-related information, and information on readiness for hospital discharge. Factors related to the need for continuing care were included in the analysis. The Readiness for Hospital Discharge Scale was used to assess the need for continuing care. The statistical data are expressed in terms of both frequency and composition ratio. Finally, linear regression was used to analyze the factors influencing the need for continuing care.

Results

The analysis included a total of 3,791 patients, 123 of whom (3.25%) had continuing nursing needs. The need of continuing nursing was related to patients’ age group, mode of admission, occupation and major diagnostic categories (P < 0.05).

Conclusions

Developing continuing care is an important initiative for bridging the fragmentation of health services, and an appropriate supply system for continuing care, interconnected with inpatient services, should be established in rural areas in China as soon as possible. And provide more appropriate care for patients in need.
Design and validation of a conceptual model regarding impact of open science on healthcare research processes
Authors: Zarghani Maryam , Nemati-Anaraki Leila , Sedghi Shahram , Chakoli Abdolreza Noroozi , Rowhani-Farid Anisa
Published: March 2024

Introduction

The development and use of digital tools in various stages of research highlight the importance of novel open science methods for an integrated and accessible research system. The objective of this study was to design and validate a conceptual model of open science on healthcare research processes.

Methods

This research was conducted in three phases using a mixed-methods approach. The first phase employed a qualitative method, namely purposive sampling and semi-structured interview guides to collect data from healthcare researchers and managers. Influential factors of open science on research processes were extracted for refining the components and developing the proposed model; the second phase utilized a panel of experts and collective agreement through purposive sampling. The final phase involved purposive sampling and Delphi technique to validate the components of the proposed model according to researchers’ perspectives.

Findings

From the thematic analysis of 20 interview on the study topic, 385 codes, 38 sub-themes, and 14 main themes were extracted for the initial proposed model. These components were reviewed by expert panel members, resulting in 31 sub-themes, 13 main themes, and 4 approved themes. Ultimately, the agreed-upon model was assessed in four layers for validation by the expert panel, and all the components achieved a score of > 75% in two Delphi rounds. The validated model was presented based on the infrastructure and culture layers, as well as supervision, assessment, publication, and sharing.

Conclusion

To effectively implement these methods in the research process, it is essential to create cultural and infrastructural backgrounds and predefined requirements for preventing potential abuses and privacy concerns in the healthcare system. Applying these principles will lead to greater access to outputs, increasing the credibility of research results and the utilization of collective intelligence in solving healthcare system issues.
Exploring the motivation of health professionals to engage with research at various career stages
Authors: D’Arrietta Louisa M. , Vangaveti Venkat N. , Crowe Melissa J. , Malau-Aduli Bunmi S.
Published: March 2024

Background

Research is crucial for improved healthcare and better patient outcomes, but there is a current shortage of clinician-researchers who can connect research and practice in the health professions field. This study aimed to investigate the effect of career stage, previous training and involvement in research on health professionals' (HPs) motivations to engage in research while in public hospital clinical roles. HPs' perceived motivation concerning the importance, value, and barriers attributed to research during different career stages were examined.

Methods

A mixed methods study design was adopted for this research. An online survey developed based on the Expectancy-Value-Cost (EVC) theory was distributed to HPs (doctors, nurses, midwives, and allied health professionals) in three North Queensland Public Hospitals. Data analysis included descriptive and inferential statistics for the quantitative data and content analysis for the qualitative text responses.

Results

Three hundred and fifty-five responses were received. Prior research training and involvement in research influenced respondents' perceptions about the importance, attitude, motivators, and barriers to research. Attainment value was the overarching motivation for involvement in research and research training for all career stages and all professional HP groups. Positive attitude to research was significantly higher (P = 0.003) for the allied health group (27.45 ± 4.05), followed by the medical (26.30 ± 4.12) and then the nursing and midwifery group (25.62 ± 4.21). Perceived importance and attitude attributed to research were significantly higher (P < 0.05) for those who had research training (26.66 ± 3.26 and 28.21 ± 3.73) compared to those who did not have research training (25.77 ± 3.77 and 23.97 ± 3.53). Significantly higher (P < 0.05) perceptions of organisational and individual barriers were reported among early career (50.52 ± 7.30) respondents compared to their mid-career (48.49 ± 8.14) and late career (47.71 ± 8.36) counterparts.

Conclusion

The findings from this study provide valuable insights into the factors that influence HPs' motivation for research. The results underscore the importance of professional group, involvement in research, exposure to research training, career stage, gender, and organisational support in shaping HPs' attitudes, values, and perceived barriers to research. Understanding these factors can inform the development of targeted strategies to enhance research engagement among HPs and promote evidence-based practice in healthcare.
Breastfeeding is associated with enhanced intestinal gluconeogenesis in infants
Authors: Ni Duan , Tan Jian , Macia Laurence , Nanan Ralph
Published: March 2024

Background

Breastfeeding (BF) confers metabolic benefits to infants, including reducing risks of metabolic syndrome such as obesity and diabetes later in life. However, the underlying mechanism is not yet fully understood. Hence, we aim to investigate the impacts of BF on the metabolic organs of infants.

Methods

Previous literatures directly studying the influences of BF on offspring’s metabolic organs in both animal models and humans were comprehensively reviewed. A microarray dataset of intestinal gene expression comparing infants fed on breastmilk versus formula milk was analyzed.

Results

Reanalysis of microarray data showed that BF is associated with enhanced intestinal gluconeogenesis in infants. This resembles observations in other mammalian species showing that BF was also linked to increased gluconeogenesis.

Conclusions

BF is associated with enhanced intestinal gluconeogenesis in infants, which may underpin its metabolic advantages through finetuning metabolic homeostasis. This observation seems to be conserved across species, hinting its biological significance.
MUC5AC concentrations in lung lavage fluids are associated with acute lung injury after cardiac surgery
Authors: van Paassen Judith , Hiemstra Pieter S. , van der Linden Abraham C. , de Jonge Evert , Zwaginga Jaap Jan , Klautz Robert J.M. , Arbous M. Sesmu
Published: March 2024

Heart surgery may be complicated by acute lung injury and adult respiratory distress syndrome. Expression and release of mucins MUC5AC and MUC5B in the lungs has been reported to be increased in acute lung injury. The aim of our study was to [1] investigate the perioperative changes of MUC5AC, MUC5B and other biomarkers in mini-bronchoalveolar lavage (minBAL), and [2] relate these to clinical outcomes after cardiac surgery. In this prospective cohort study in 49 adult cardiac surgery patients pre- and post-surgery non-fiberscopic miniBAL fluids were analysed for MUC5AC, MUC5B, IL-8, human neutrophil elastase, and neutrophils. All measured biomarkers increased after surgery. Perioperative MUC5AC-change showed a significant negative association with postoperative P/F ratio (p = 0.018), and a positive association with ICU stay (p = 0.027). In conclusion, development of lung injury after cardiac surgery and prolonged ICU stay are associated with an early increase of MUC5AC as detected in mini-BAL.