bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of fertility restoration candidate genes from a restorer line R186 for Gossypium harknessii cytoplasmic male sterile cotton
Authors: Cheng Cheng , Nie Hushuai , Li Huijing , Adjibolosoo Daniel , Li Bin , Jiang Kaiyun , Cui Yanan , Zhu Meng , Zhou Baixue , Guo Anhui , Hua Jinping
Published: April 2023

Background

The utilization of heterosis based on three-line system is an effective strategy in crop breeding. However, cloning and mechanism elucidation of restorer genes for cytoplasmic male sterility (CMS) in upland cotton have yet been realized.

Results

This research is based on CMS line 2074A with the cytoplasm from Gossypium harknessii (D2-2) and restorer line R186. The offspring of 2074A × R186 were used to conduct genetic analysis. The fertility mechanism of 2074A can be speculated to be governed by multiple genes, since neither the single gene model nor the double genes model could be used. The bulked segregant analysis (BSA) for (2074A × R186) F2 determined the genetic interval of restorer genes on a region of 4.30 Mb on chromosome D05 that contains 77 annotated genes. Four genes were identified as candidates for fertility restoration using the RNA-seq data of 2074A, 2074B, and R186. There are a number of large effect variants in the four genes between 2074A and R186 that could cause amino acid changes. Evolutionary analysis and identity analysis revealed that GH_D05G3183, GH_D05G3384, and GH_D05G3490 have high identity with their homologs in D2-2, respectively. Tissue differential expression analysis revealed that the genes GH_D05G3183, GH_D05G3384, and GH_D05G3490 were highly expressed in the buds of the line R186. The predicted results demonstrated that GH_D05G3183, GH_D05G3384 and GH_D05G3490 might interact with GH_A02G1295 to regulate orf610a in mitochondria.

Conclusion

Our study uncovered candidate genes for fertility restoration in the restorer line R186 and predicted the possible mechanism for restoring the male fertility in 2074A. This research provided valuable insight into the nucleoplasmic interactions.
Quality of systematic reviews on timing of complementary feeding for early childhood allergy prevention
Authors: Matterne Uwe , Theurich Melissa A. , Pröbstl Simone , Pieper Dawid , Wang Jiancong , Xu Anna , Apfelbacher Christian
Published: April 2023

Background

Only rigorously prepared analyses can provide the highest level of evidence to inform decision-making. Several recent systematic reviews (SRs) examined the hypothesis that the early introduction of specific allergenic complementary foods (CFs) to infants may lead to a lower incidence of one or more allergic outcomes. However, the methodological rigour and quality of reporting of SRs in this area has not yet been systematically evaluated.

Methods

We comprehensively searched PubMed, Medline (Ovid), and Web of Science Core Collection on 13th January 2022, using a pre-specified and tested search syntax for SRs with RCT evidence on the early introduction of allergenic CFs as a means for allergy prevention in infants and children. We examined the quality and risk of bias (RoB) using AMSTAR-2 and ROBIS tools, examined adherence to the Preferred Reporting Items for SRs and Meta-Analyses (PRISMA), and checked whether certainty of the evidence was assessed.

Results

Twelve SRs were included. Application of both tools resulted in similar overall judgements in terms of direction and extent for nine of the 12 SRs. Nine SRs were found to be of critically low to low quality according to AMSTAR-2 and to be at high RoB according to ROBIS. One SR received a moderate quality rating (AMSTAR-2) and high RoB rating (ROBIS). However, for two SRs, judgements between AMSTAR-2 and ROBIS were at stark variance. Only two SRs fully adhered to the PRISMA checklist. Six SRs evaluated the certainty of the body of RCT evidence. Several SRs failed to consider unpublished studies either by an explicit a priori exclusion or by inadequate search strategies.

Conclusions

Well-conducted SRs are important for decision-making and informing guideline development, the quality of their methodology should therefore be considered. The methodological rigour and the reporting quality of SRs on the timing of CF for allergy prevention must be improved.

Registration

https://osf.io/7cs4b.
Atrial fibrillation incidence and outcomes in two cohorts of octogenarians: LiLACS NZ
Authors: Teh Ruth , Kerse Ngaire , Pillai Avinesh , Lumley Thomas , Rolleston Anna , Kyaw Tin Aung , Connolly Martin , Broad Joanna , Monteiro Elaine , Clair Valerie Wright-St , Doughty Robert N.
Published: April 2023

Background

Atrial fibrillation (AF), the most common cardiac arrhythmia in the general population, has significant healthcare burden. Little is known about AF in octogenarians.

Objective

To describe the prevalence and incidence rate of AF in New Zealand (NZ) octogenarians and the risk of stroke and mortality at 5-year follow-up.

Design

Longitudinal Cohort Study.

Setting

Bay of Plenty and Lakes health regions of New Zealand.

Subjects

Eight-hundred-seventy-seven (379 indigenous Māori, 498 non-Māori) were included in the analysis.

Methods

AF, stroke/TIA events and relevant co-variates were established annually using self-report and hospital records (and ECG for AF). Cox proportional-hazards regression models were used to determine the time dependent AF risk of stroke/TIA.

Results

AF was present in 21% at baseline (Māori 26%, non-Māori 18%), the prevalence doubled over 5-years (Māori 50%, non-Māori 33%). 5-year AF incidence was 82.6 /1000-person years and at all times AF incidence for Māori was twice that of non-Māori. Five-year stroke/TIA prevalence was 23% (22% in Māori and 24% non- Māori), higher in those with AF than without. AF was not independently associated with 5-year new stroke/TIA; baseline systolic blood pressure was. Mortality was higher for Māori, men, those with AF and CHF and statin use was protective.

In summary, AF is more prevalent in indigenous octogenarians and should have an increased focus in health care management. Further research could examine treatment in more detail to facilitate ethnic specific impact and risks and benefits of treating AF in octogenarians.
Development of a personalized fall rate prediction model in community-dwelling older adults: a negative binomial regression modelling approach
Authors: Wapp Christina , Biver Emmanuel , Ferrari Serge , Zysset Philippe , Zwahlen Marcel
Published: April 2023

Background

Around a third of adults aged 65 and older fall every year, resulting in unintentional injuries in 30% of the cases. Fractures are a frequent consequence of falls, primarily caused in individuals with decreased bone strength who are unable to cushion their falls. Accordingly, an individual’s number of experienced falls has a direct influence on fracture risk. The aim of this study was the development of a statistical model to predict future fall rates using personalized risk predictors.

Methods

In the prospective cohort GERICO, several fall risk factor variables were collected in community-dwelling older adults at two time-points four years apart (T1 and T2). Participants were asked how many falls they experienced during 12 months prior to the examinations. Rate ratios for the number of reported falls at T2 were computed for age, sex, reported fall number at T1, physical performance tests, physical activity level, comorbidity and medication number with negative binomial regression models.

Results

The analysis included 604 participants (male: 122, female: 482) with a median age of 67.90 years at T1. The mean number of falls per person was 1.04 and 0.70 at T1 and T2. The number of reported falls at T1 as a factor variable was the strongest risk factor with an unadjusted rate ratio [RR] of 2.60 for 3 falls (95% confidence interval [CI] 1.54 to 4.37), RR of 2.63 (95% CI 1.06 to 6.54) for 4 falls, and RR of 10.19 (95% CI 6.25 to 16.60) for 5 and more falls, when compared to 0 falls. The cross-validated prediction error was comparable for the global model including all candidate variables and the univariable model including prior fall numbers at T1 as the only predictor.

Conclusion

In the GERICO cohort, the prior fall number as single predictor information for a personalized fall rate is as good as when including further available fall risk factors. Specifically, individuals who have experienced three and more falls are expected to fall multiple times again.

Trial registration

ISRCTN11865958, 13/07/2016, retrospectively registered.
The impact of ethnic background on ICU care and outcome in sepsis and septic shock – A retrospective multicenter analysis on 17,949 patients
Authors: Koköfer Andreas , Mamandipoor Behrooz , Flamm Maria , Rezar Richard , Wernly Sarah , Datz Christian , Jung Christian , Osmani Venet , Wernly Bernhard , Bruno Raphael Romano
Published: April 2023

Background

Previous studies have been inconclusive about racial disparities in sepsis. This study evaluated the impact of ethnic background on management and outcome in sepsis and septic shock.

Methods

This analysis included 17,146 patients suffering from sepsis and septic shock from the multicenter eICU Collaborative Research Database. Generalized estimated equation (GEE) population-averaged models were used to fit three sequential regression models for the binary primary outcome of hospital mortality.

Results

Non-Hispanic whites were the predominant group (n = 14,124), followed by African Americans (n = 1,852), Hispanics (n = 717), Asian Americans (n = 280), Native Americans (n = 146) and others (n = 830). Overall, the intensive care treatment and hospital mortality were similar between all ethnic groups.This finding was concordant in patients with septic shock and persisted after adjusting for patient-level variables (age, sex, mechanical ventilation, vasopressor use and comorbidities) and hospital variables (teaching hospital status, number of beds in the hospital).

Conclusion

We could not detect ethnic disparities in the management and outcomes of critically ill septic patients and patients suffering from septic shock. Disparate outcomes among critically ill septic patients of different ethnicities are a public health, rather than a critical care challenge.
Shift from severe hypotension to salt-dependent hypertension in a child with autosomal recessive polycystic kidney disease after bilateral nephrectomies: a case report
Authors: Ruzgiene Dovile , Abraityte Lauryna , Azukaitis Karolis , Liebau Max Christoph , Jankauskiene Augustina
Published: April 2023

Background

Autosomal recessive polycystic kidney disease (ARPKD) is a significant cause of morbidity and mortality in infants and children. In severe cases bilateral nephrectomies are considered but may be associated with significant neurological complications and life-threatening hypotension.

Case presentation

We describe a case of a 17 months old boy with genetically confirmed ARPKD who underwent sequential bilateral nephrectomies at the age of 4 and 10 months. Following the second nephrectomy the boy was started on continuous cycling peritoneal dialysis with blood pressure on the lower range. At the age of 12 months after a few days of poor feeding at home the boy experienced a severe episode of hypotension and coma of Glasgow Come Scale of three. Brain magnetic-resonance imaging (MRI) showed signs of hemorrhage, cytotoxic cerebral edema and diffuse cerebral atrophy. During the subsequent 72 h he developed seizures requiring anti-epileptic drug therapy, gradually regained consciousness but remained significantly hypotensive after discontinuation of vasopressors. Thus, he received high doses of sodium chloride orally and intraperitoneally as well as midodrine hydrochloride. His ultrafiltration (UF) was targeted to keep him in mild-to-moderate fluid overload. After two months of stable condition the patient started to develop hypertension requiring four antihypertensive medications. After optimizing peritoneal dialysis to avoid fluid overload and discontinuation of sodium chloride the antihypertensives were discontinued, but hyponatremia with hypotensive episodes reoccurred. Sodium chloride was reintroduced resulting in recurrent salt-dependent hypertension.

Conclusions

Our case report illustrates an unusual course of blood pressure changes following bilateral nephrectomies in an infant with ARPKD and the particular importance of tight regulation of sodium chloride supplementation. The case adds to the scarce literature about clinical sequences of bilateral nephrectomies in infants, and as well highlights the challenge of managing blood pressure in these patients. Further research on the mechanisms and management of blood pressure control is clearly needed.
Epidemiology and patient journey of Rett syndrome in the United States: a real-world evidence study
Authors: May Damian , Kponee-Shovein Kalé , Mahendran Malena , Downes Nathaniel , Sheng Kristy , Lefebvre Patrick , Cheng Wendy Y.
Published: April 2023

Background

Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females and is associated with high clinical burden. However, literature characterizing the real-world journey of patients with RTT is limited. This study provided an overview of the epidemiology, patient characteristics, clinical manifestations, healthcare resource utilization (HRU), costs, and treatment patterns of patients with RTT in the US.

Methods

IQVIA™ Medical Claims Data and Longitudinal Prescription Data (11/01/2016–10/31/2019) were used to identify female patients with RTT, with the first observed diagnosis defined as the index date. Annual incidence and prevalence of RTT were assessed over the entire study period; clinical manifestations, all-cause and RTT-related HRU and costs, and treatment patterns were evaluated during the observation period—from the index date to end of clinical activity or end of data availability, whichever occurred first. Results were further stratified into pediatric (< 18 years) and adult (≥ 18 years) subgroups.

Results

In 2019, prevalence and incidence of RTT was 0.32 and 0.23 per 10,000 enrollees, respectively. Among 5,940 female patients (pediatric: 3,078; adult: 2,862) with mean observation period of 2.04 years, the most prevalent clinical manifestations were neurological disorders (72.8%), gastrointestinal/nutritional disorders (41.9%), and orthopedic disorders (34.6%). The incidence rate of all-cause HRU was 44.43 visits per-patient-per-year and RTT-related HRU comprised 47% of all-cause HRU. Mean all-cause healthcare costs were $40,326 per-patient-per-year, with medical costs driven by home/hospice care visits, therapeutic services, outpatient visits, and inpatient visits. RTT-related healthcare costs comprised 45% of all-cause healthcare costs. The most prevalent supportive therapy and pharmacologic agent were feeding assistance (37.9%) and antiepileptic drugs (54.8%), respectively. Trends were similar by subgroup; although, rates of HRU were generally higher among pediatric patients relative to adult patients (all-cause: 52.43 and 35.86, respectively), which translated into higher mean healthcare costs (all-cause: $45,718 and $34,548, respectively).

Conclusions

Patients with RTT have substantial disease burden, including prevalent clinical manifestations, high rates of HRU and annual healthcare costs, and reliance on pharmacologic and supportive therapies. These findings underscore the unmet need for effective therapies to target the multifactorial manifestations of RTT.
Exploring physicians’ prescribing behavior in patients with multiple sclerosis in Saudi Arabia: a sequential explanatory mixed-methods
Authors: Al-Omar Hussain Abdulrahman , Alsowaida Nada , Aldosari Lama , Mayet Ahmed , Bunyan Reem , Aljumah Mohammed
Published: April 2023

Background

Multiple sclerosis (MS) is the most common disabling neurological disease in young adults worldwide with majority of patients manifest symptoms between 20 and 40 years of age. The aims of this study are to explore physicians’ perspectives, views, and behaviors in diagnosing and treating patients with MS in Saudi Arabia and investigate the prescribing pattern of disease-modifying therapies (DMTs).

Methods

A sequential explanatory mixed-method approach was used to achieve the study objectives. The quantitative arm of the study consisted of patient data extracted from the Saudi MS registry from 2015 to 2018. The qualitative study consisted of in-depth semi-structured interviews with physicians using a validated interview topic guide comprising 28 open-ended questions.

Results

We extracted data of 2,507 patients from 20 different hospitals across Saudi Arabia. Patients’ mean age was 34 ± 10 years; two-thirds (n = 1,668) were female. 92% (n = 2,292) had relapsing-remitting multiple sclerosis, and 5% (n = 126) had secondary-progressive multiple sclerosis. In general, patients with MS received at least one drug as the DMT or DMTs and corticosteroids for those with relapse. Qualitatively, nine physicians agreed to participate in the interviews. Of them, five (55%) were male and four were female from different regions. Thematic analysis yielded three main themes: practice, views, and challenges.

Conclusions

The prevalence of MS in Saudi Arabia is raising but is still much lower than that reported in the Gulf region. A national MS guideline is needed to streamline diagnosis and treatment criteria, avoid any delay in treatment, and guide physicians who provide care for patients with MS.
Gadolinium enhancement in cervical dorsal roots in a patient with acute autonomic and sensory neuropathy: a case report
Authors: Kim Du Hwan , Cho Jang Hyuk , Boudier-Revéret Mathieu , Chang Min Cheol
Published: April 2023

Background

We report an enhancement of the dorsal roots on gadolinium-enhanced cervical magnetic resonance imaging (MRI) in a patient with acute autonomic and sensory neuropathy (AASN).

Case presentation

A 38-year-old woman visited our university hospital for dizziness and fainting while rising from sitting or lying down and a tingling sensation in the whole body, including her limbs, torso, and abdomen, which was sustained for 15 days. The patient had hyperalgesia in nearly her entire body and slight motor weakness in her bilateral upper and lower limbs. Autonomic dysfunction was confirmed using autonomic testing. Furthermore, the nerve conduction study showed an absence of sensory nerve action potentials in all evaluated peripheral nerves. Cervical MRI was performed 18 days after dysautonomia onset. In the axial T1-gadolinum-enhanced MRIs, enhancement in cervical ventral and dorsal nerve roots and the posterior column of the spinal cord were observed, and the axial T2-weighted MRI showed high signal intensity in the posterior column of the cervical spinal cord. Considering the clinical, electrophysiological and imaging findings, the patient was diagnosed with AASN. A total dose of 90 g (2 g/kg) of intravenous immunoglobulin was administered over 5 days. At the follow-up at 4 years after AASN symptom onset, the hyperalgesia and orthostatic hypotension symptoms improved. However, her systolic blood pressure intermittently decreased to < 80 mmHg.

Conclusion

Gadolinium-enhanced MRI may facilitate the accurate and prompt diagnosis of AASN.
Association of polygenic risk score with response to deep brain stimulation in Parkinson’s disease
Authors: Yoon Esther , Ahmed Sarah , Li Ryan , Bandres-Ciga Sara , Blauwendraat Cornelis , Dustin Irene , Scholz Sonja , Hallett Mark , Ehrlich Debra
Published: April 2023

Background

Deep brain stimulation (DBS) is a well-established treatment option for select patients with Parkinson’s Disease (PD). However, response to DBS varies, therefore, the ability to predict who will have better outcomes can aid patient selection. Some PD-related monogenic mutations have been reported among factors that influence response to DBS. However, monogenic disease accounts for only a minority of patients with PD. The polygenic risk score (PRS) is an indication of cumulative genetic risk for disease. The PRS in PD has also been correlated with age of onset and symptom progression, but it is unknown whether correlations exist between PRS and DBS response. Here, we performed a pilot study to look for any such correlation.

Methods

We performed a retrospective analysis of 33 PD patients from the NIH PD Clinic and 13 patients from the Parkinson’s Progression Markers Initiative database who had genetic testing and underwent bilateral subthalamic nucleus DBS surgery and clinical follow-up. A PD-specific PRS was calculated for all 46 patients based on the 90 susceptibility variants identified in the latest PD genome-wide association study. We tested associations between PRS and pre- and post-surgery motor and cognitive measures using multiple regression analysis for up to two years after surgery.

Results

Changes in scores on the Beck Depression Inventory (BDI) were not correlated with PRS when derived from all susceptibility variants, however, when removing pathogenic and high-risk carriers from the calculation, higher PRS was significantly associated with greater reduction in BDI score at 3 months and with similar trend 24 months after DBS. PRS was not a significant predictor of Unified Parkinson’s Disease Rating Scale, Dementia Rating Scale, or phenomic and semantic fluency outcomes at 3- and 24-months after DBS surgery.

Conclusions

This exploratory study suggests that PRS may predict degree of improvement in depressive symptoms after DBS, though was not predictive of motor and other cognitive outcomes after DBS. Additionally, PRS may be most relevant in predicting DBS outcomes in patients lacking pathogenic or high-risk PD variants. However, this was a small preliminary study and response to DBS treatment is multifactorial, therefore, more standardized high-powered studies are needed.
Association between poor parent-daughter relationships and the risk of hyperglycemia in pregnancy: a hospital-based prospective cohort study in Japan
Authors: Maeda Yuto , Doi Satomi , Isumi Aya , Terada Shuhei , Sugawara Junichi , Maeda Kazuhisa , Satoh Shoji , Mitsuda Nobuaki , Fujiwara Takeo
Published: April 2023

Background

Adverse child experiences (ACEs), childhood maltreatment and household dysfunction, are risk factors of hyperglycemia in pregnancy (HIP), including diabetes before pregnancy, gestational diabetes (GDM), and overt diabetes in pregnancy, through increased risk of unhealthy behaviors, obesity, and stress response system dysfunction. While ACEs are often difficult to be assessed in hospital settings, parent-daughter relationship, that is, pregnant women’s relationship with their parents can be considered as a measurable maker for ACEs that may be associated with HIP. The purpose of this study is to examine the association between poor parent-daughter relationship and HIP.

Methods

Hospital-based prospective cohort study was conducted in Japan (N = 6,264). Women visiting participating 58 facilities for delivery between April 2019 and March 2020 were included. Parent-daughter relationship was assessed by a questionnaire asking whether participants were satisfied with their relationship with their parents. HIP was diagnosed based on the criteria used in Japan. A multiple logistic regression model was applied to adjust for covariates.

Results

Pregnant women who were not very satisfied and not satisfied at all with the relationship with their parents, and HIP were 343 (5.5%), 74 (1.2%), and 274 (4.4%), respectively. Pregnant women who were not very satisfied with their parent-daughter relationship showed a significant positive association with HIP in the crude model (odds ratio (OR): 1.71, 95% confidence interval (CI): 1.11–2.63). When stratified by psychiatric disease history, we found a significant positive association among those without psychiatric disease history (OR: 1.77, 95% CI: 1.11–2.84), but not among those with psychiatric disease history (OR: 0.61, 95% CI: 0.16–2.28).

Conclusions

Poor parent-daughter relationship was associated with the risk of HIP among pregnant women without psychiatric disease history, suggesting that this simple question could be used to estimate the risk of HIP when it was challenging to inquire directly about ACEs. Further research is needed to elucidate the mechanism of the association.
Does resection after neoadjuvant chemotherapy of docetaxel, oxaliplatin, and S-1 (DOS regimen) benefit for gastric cancer patients with single non-curable factor? a multicenter, prospective cohort study (Neo-REGATTA)
Authors: Cui Yuehong , Yu Yiyi , Zheng Song , Ying Jie’er , Du Yi’an , Wang Yan , Wang Xuefei , Shen Zhenbin , Liu Fenglin , Lv Minzhi , Sun Yihong , Liu Tianshu
Published: April 2023

Background

The Neo-REGATTA study evaluated the effectiveness and safety of Docetaxel, oxaliplatin, and S-1 (DOS regimen) followed by radical resection vs. chemotherapy in advanced gastric adenocarcinoma patients with single non-curable factor.

Methods

This cohort study prospectively enrolled advanced gastric adenocarcinoma patients with single non-curable factor between November 2017 and June 2021. Patients without progression after four cycles of DOS were divided into resection group and chemotherapy group. The outcomes included overall survival (OS), progression-free survival (PFS) and safety. Effectiveness analysis was also performed by propensity score matching (PSM).

Results

A total of 73 patients were enrolled and 13 patients were withdrawn due to disease progression after 4 cycles of DOS. Afterwards, 35 and 25 participants were in the resection and chemotherapy groups, respectively. After a median follow-up time of 30.0 months, the median PFS and OS were 9.0 months, and 18.0 months for the chemotherapy group, but not reached in the resection group. After PSM, 19 matched participants were in each group, and the median PFS and OS were longer in resection group than that in chemotherapy group. The most common grade 3 or 4 adverse events both in the resection group and chemotherapy groups were neutropenia (5.7%, 8.0%) and leukopenia (5.7%, 8.0%).

Conclusions

Radical resection might provide survival benefit compared with continuous chemotherapy alone in advanced gastric adenocarcinoma patients who had a disease control after DOS, with a good safety profile.

Trial registration

The study protocol was registered on ClinicalTrial.gov (NCT03001726, 23/12/2016).
Activity and safety of KEES - an oral multi-drug chemo-hormonal metronomic combination regimen in metastatic castration-resistant prostate cancer
Authors: Asowed Mustafa , Elander Nils O , Pettersson Linn , Ekholm Maria , Papantoniou Dimitrios
Published: April 2023

Background

Metastatic castration-resistant prostate cancer (mCRPC) remains a therapeutic challenge and evidence for late-line treatments in real-life is limited. The present study investigates the efficacy and safety of an oral metronomic chemo-hormonal regimen including cyclophosphamide, etoposide, estramustine, ketoconazole and prednisolone (KEES) administered in a consecutive biweekly schedule.

Methods

A retrospective cohort study in two Swedish regions was conducted. Overall (OS) and progression-free survival (PFS), biochemical response rate (bRR) and toxicities were analyzed.

Results

One hundred and twenty-three patients treated with KEES after initial treatment with at least a taxane or an androgen-receptor targeting agents (ARTA) were identified. Of those, 95 (77%) had received both agents and were the primary analysis population. Median (95% CI) OS and PFS in the pre-treated population were 12.3 (10.1–15.0) and 4.4 (3.8–5.5) months, respectively. Biochemical response, defined as ≥ 50% prostate-specific antigen (PSA) reduction, occurred in 26 patients (29%), and any PSA reduction in 59 (65%). PFS was independent of prior treatments used, and KEES seemed to be effective in late treatment lines. The bRR was higher compared to historical data of metronomic treatments in docetaxel and ARTA pre-treated populations. In multivariable analyses, performance status (PS) ≥ 2 and increasing alkaline phosphatase (ALP) predicted for worse OS. Nausea, fatigue, thromboembolic events and bone marrow suppression were the predominant toxicities.

Conclusions

KEES demonstrated meaningful efficacy in heavily pre-treated CRPC patients, especially those with PS 0–1 and lower baseline ALP, and had an acceptable toxicity profile.
KIF2C is a prognostic biomarker associated with immune cell infiltration in breast cancer
Authors: Liu Shanshan , Ye Ziwei , Xue Vivian Weiwen , Sun Qi , Li Huan , Lu Desheng
Published: April 2023

Background

The kinesin-13 family member 2C (KIF2C) is a versatile protein participating in many biological processes. KIF2C is frequently up-regulated in multiple types of cancer and is associated with cancer development. However, the role of KIF2C in immune cell infiltration of tumor microenvironment and immunotherapy in breast cancer remains unclear.

Methods

The expression of KIF2C was analyzed using Tumor Immune Estimation Resource (TIMER) database and further verified by immunohistochemical staining in human breast cancer tissues. The correlation between KIF2C expression and clinical parameters, the impact of KIF2C on clinical prognosis and independent prognostic factors were analyzed by using TCGA database, the Kaplan-Meier plotter, and Univariate and multivariate Cox analyses, respectively. The nomograms were constructed according to independent prognostic factors and validated with C-index, calibration curves, ROC curves, and decision curve analysis. A gene set enrichment analysis (GSEA) was performed to explore the underlying molecular mechanisms of KIF2C. The degree of immune infiltration was assessed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression (ESTIMATE) algorithm and the single sample GSEA (ssGSEA). The Tumor mutational burden and Tumor Immune Dysfunction and Rejection (TIDE) were used to analyze immunotherapeutic efficiency. Finally, the KIF2C-related competing endogenous RNA (ceRNA) network was constructed to predict the putative regulatory mechanisms of KIF2C.

Results

KIF2C was remarkably up-regulated in 18 different types of cancers, including breast cancer. Kaplan-Meier survival analysis showed that high KIF2C expression was associated with poor overall survival (OS). KIF2C expression was associated with clinical parameters such as age, TMN stage, T status, and molecular subtypes. We identified age, stage, estrogen receptor (ER) and KIF2C expression as OS-related independent prognosis factors for breast cancer. An OS-related nomogram was developed based on these independent prognosis factors and displayed good predicting ability for OS of breast cancer patients. Finally, our results revealed that KIF2C was significantly related to immune cell infiltration, tumor mutational burden, and immunotherapy in patients with breast cancer.

Conclusion

KIF2C was overexpressed in breast cancer and was positively correlated with immune cell infiltration and immunotherapy response. Therefore, KIF2C can serve as a potential biomarker for prognosis and immunotherapy in breast cancer.
White-Sutton syndrome and congenital heart disease: case report and literature review
Authors: Duan Jing , Ye Yuanzhen , Liao Jianxiang , Chen Li , Zhao Xia , Liu Chao , Wen Jialun
Published: April 2023

Background

White-Sutton syndrome is an autosomal dominant neurodevelopmental disorder caused by heterozygous mutation inPOGZ(Pogo Transposable Element Derived with ZNF Domain). This syndrome is characterized by delayed psychomotor development apparent in infancy and abnormal facial features. To date, 80 cases have been reported in the literature; however, the phenotypic characterizations remain incomplete.

Case presentation

We herein describe a 2-year-old girl harboring a novel frameshift de novoPOGZvariant: c.2746del (p.Thr916ProfsTer12). This patient presented with multisystem abnormalities affecting the digestive tract and neurological functioning, as well as congenital heart disease, which involved an atrial septal defect (18 × 23 × 22 mm) with pulmonary arterial hypertension (42 mmHg). The relationship between congenital heart disease and White-Sutton syndrome as described in both the GeneReview and OMIM databases (#616,364) remains unclear. A review of the current literature revealed 18 cases of White-Sutton syndrome withPOGZvariants and congenital heart disease, and we summarize their clinical features in this study.

Conclusions

Our findings based on the present case and those in the literature indicate a relationship betweenPOGZmutation and congenital heart disease.
Nutritional counselling in adults promoting adherence to the Mediterranean diet as adjuvant in the treatment of major depressive disorder (INDEPT): a randomized open controlled trial study protocol
Authors: Sousa-Santos Nuno , Fialho Mónica , Madeira Teresa , Clara Cátia , Veiga Sofia , Martins Raquel , Barros Neuza , Santos Gabriela , Santos Osvaldo , Almeida Carolina , Ganança Licínia , Campos Rui C. , Camolas José , da Silva Alda Pereira , Guarino Maria Pedro Sucena , Heitor Maria João
Published: April 2023

Background

Major Depressive Disorder (MDD) is a leading cause of disability worldwide. Approximately one-third of patients with MDD do not respond to treatment, and often exhibit elevated inflammation biomarkers, which are associated with worse prognosis. Previous research has linked healthier dietary patterns, such as the Mediterranean Diet (MedDiet), with a lower risk of MDD and symptoms of depression, potentially due to their anti-inflammatory properties. The aim of this study is to evaluate the effectiveness of a nutritional counselling intervention promoting MedDiet to alleviate symptoms of depression in adults recently diagnosed with MDD and presenting with elevated inflammation biomarkers.

Methods

This study is a randomized controlled trial (RCT) that will recruit adults from outpatient clinics, between the ages of 18 and 70 years who have been diagnosed with MDD and are currently receiving treatment with the first prescribed antidepressant, and who exhibit elevated inflammation biomarkers (interleukin-6 and/or C-reactive protein). The control group will receive treatment-as-usual (TAU) only. The primary outcome of the study will be the change in symptoms of depression, as measured by the Beck Depression Inventory 2 (BDI-II), after 12 weeks of intervention. Data analysis will follow an intention-to-treat approach. Secondary outcomes will include changes in inflammation biomarkers, quality of life, adherence to the MedDiet, and cost-effectiveness of nutritional counselling. All outcomes will be assessed at baseline, after the 12-week intervention, and at 6- and 12-months post-baseline.

Discussion

This study will be the first RCT to evaluate the effect of a nutritional intervention with anti-inflammatory properties, as an adjuvant in the treatment of MDD, in individuals diagnosed with MDD and elevated inflammation biomarkers. The results of this study may contribute to the development of more effective and personalized interventions for MDD patients with elevated inflammation biomarkers.
Trend analysis of multi-level determinants of maternal and newborn postnatal care utilization in Pakistan from 2006 to 2018: Evidence from Pakistan Demographic and Health Surveys
Authors: Iqbal Sarosh , Maqsood Sidra , Zakar Rubeena , Fischer Florian
Published: April 2023

Background

Postnatal care (PNC) is crucial for maternal and newborn health. Healthcare-seeking practices within the postpartum period help healthcare providers in early detection of complications related to childbirth and post-delivery period. This study aims to investigate trends of PNC utilization from 2006 to 2018, and to explore the effects of multi-level determinants of both maternal and newborn PNC in Pakistan.

Methods

Secondary data analysis of the last three waves of the nationally representative Pakistan Demographic and Health Surveys (PDHSs) was conducted Analysis was limited to all those women who had delivered a child during the last 5 years preceding each wave of PDHS Bivariate and multivariate logistic regression was applied to determine the association of maternal and newborn PNC utilization with multi-level determinants at individual, community, and institutional levels.

Results

In Pakistan, an upward linear trend in maternal PNC utilization was found, with an increase from 43.5 to 63.6% from 2006 to 2018. However, a non-linear trend was observed in newborn PNC utilization, with an upsurge from 20.6 to 50.5% from 2006 to 2013, nonetheless a decrease of 30.7% in 2018. Furthermore, the results highlighted that the likelihood of maternal and newborn PNC utilization was higher amongst older age women, who completed some years of schooling, were employed, had decision-making and emotional autonomy, had caesarean sections, and delivered at health facilities by skilled birth attendants. Multivariate analysis also revealed higher odds for women of older age, who had decision-making and emotional autonomy, and had caesarean section deliveries over the period of 2006–2018 for both maternal and newborn PNC utilization. Further, higher odds for maternal PNC utilization were found with parity and size of newborn, while less for ANC attendance and available means of transportation. Furthermore, increased odds were recorded for newborn PNC utilization with the number of children, ANC attendance, gender of child and mass media exposure from 2006 to 18.

Conclusion

A difference in maternal and newborn PNC utilization was found in Pakistan, attributed to multiple individual (socio-demographic and obstetrics), community, and institutional level determinants. Overall, findings suggest the need to promote the benefits of PNC for early diagnosis of postpartum complications and to plan effective public health interventions to enhance women’s access to healthcare facilities and skilled birth assistance to save mothers’ and newborns’ lives.
Financial stress as a mediator of the association between maternal childhood adversity and infant birth weight, gestational age, and NICU admission
Authors: Sosnowski David W. , Ellison-Barnes Alejandra , Kaufman Joan , Hoyo Cathrine , Murphy Susan K. , Hernandez Raquel G. , Marchesoni Joddy , Klein Lauren M. , Johnson Sara B.
Published: April 2023

Background

To examine whether financial stress during pregnancy mediates the association between maternal exposure to adverse childhood experiences (ACEs) and three birth outcomes (i.e., gestational age, birth weight, and admission to the neonatal intensive care unit [NICU]).

Methods

Data were obtained from a prospective cohort study of pregnant women and their infants in Florida and North Carolina. Mothers (n = 531; Mage at delivery = 29.8 years; 38% Black; 22% Hispanic) self-reported their exposure to childhood adversity and financial stress during pregnancy. Data on infant gestational age at birth, birth weight, and admission to the NICU were obtained from medical records within 7 days of delivery. Mediation analysis was used to test study hypotheses, adjusting for study cohort, maternal race, ethnicity, body mass index, and tobacco use during pregnancy.

Results

There was evidence of an indirect association between maternal exposure to childhood adversity and infant gestational age at birth (b = -0.03, 95% CI = -0.06 – -0.01) and infant birth weight (b = -8.85, 95% CI = -18.60 – -1.28) such that higher maternal ACE score was associated with earlier gestational age and lower infant birth weight through increases in financial distress during pregnancy. There was no evidence of an indirect association between maternal exposure to childhood adversity and infant NICU admission (b = 0.01, 95% CI = -0.02–0.08).

Conclusions

Findings demonstrate one pathway linking maternal childhood adversity to a potentially preterm birth or shorter gestational age, in addition to low birth weight at delivery, and present an opportunity for targeted intervention to support expecting mothers who face financial stress.
Taking control of one’s everyday life - a qualitative study of experiences described by participants in an occupational intervention
Authors: Karlsson Louise , Erlandsson Lena-Karin , Cregård Anna , Nordgren Lena , Lydell Marie
Published: April 2023

Background

Sick leave due to stress-related ill-health is increasing and is often caused by occupational imbalance. These types of issues tend to affect both the ability to work and cope with everyday life, as well as the overall experience of health, negatively. There is still little knowledge on how to prepare people and workplaces for the return-to-work process after participation in a work rehabilitation program due to stress and occupational ill-health. Therefore, this study aimed to describe what is needed to achieve a balanced everyday life that includes paid work as experienced by individuals who had participated in a ReDO® intervention due to occupational imbalance and ill-health.

Methods

The concluding notes from 54 informants’ medical records were used for qualitative content analysis. The informants had participated in an occupational therapy group intervention to promote occupational health and regain full work capacity.

Results

The analysis resulted in one major theme and four categories describing how the informants perceive that they must take control of their everyday life as a whole. By doing so, they need to work with structurization and prioritization, social interaction, boundary setting, and occupational meaningfulness.

Conclusion

The study indicates a highly relational process, where it is impossible to divide life into private and work, and presupposes balance in everyday life in multiple dimensions. Its contribution includes the formulation of perceived needs in the transition between intervention and return to work and could, through further research, be used to generate a more effective and sustainable return- and rehabilitation models.
Research on hand, foot and mouth disease incidence forecasting using hybrid model in mainland China
Authors: Zhao Daren , Zhang Huiwu , Zhang Ruihua , He Sizhang
Published: April 2023

Background

This study aimed to construct a more accurate model to forecast the incidence of hand, foot, and mouth disease (HFMD) in mainland China from January 2008 to December 2019 and to provide a reference for the surveillance and early warning of HFMD.

Methods

We collected data on the incidence of HFMD in mainland China between January 2008 and December 2019. The SARIMA, SARIMA-BPNN, and SARIMA-PSO-BPNN hybrid models were used to predict the incidence of HFMD. The prediction performance was compared using the mean absolute error(MAE), mean squared error(MSE), root mean square error (RMSE), mean absolute percentage error (MAPE), and correlation analysis.

Results

The incidence of HFMD in mainland China from January 2008 to December 2019 showed fluctuating downward trends with clear seasonality and periodicity. The optimal SARIMA model was SARIMA(1,0,1)(2,1,2)[12], with Akaike information criterion (AIC) and Bayesian Schwarz information criterion (BIC) values of this model were 638.72, 661.02, respectively. The optimal SARIMA-BPNN hybrid model was a 3-layer BPNN neural network with nodes of 1, 10, and 1 in the input, hidden, and output layers, and the R-squared, MAE, and RMSE values were 0.78, 3.30, and 4.15, respectively.

For the optimal SARIMA-PSO-BPNN hybrid model, the number of particles is 10, the acceleration coefficients c1 and c2 are both 1, the inertia weight is 1, the probability of change is 0.95, and the values of R-squared, MAE, and RMSE are 0.86, 2.89, and 3.57, respectively.

Conclusions

Compared with the SARIMA and SARIMA-BPNN hybrid models, the SARIMA-PSO-BPNN model can effectively forecast the change in observed HFMD incidence, which can serve as a reference for the prevention and control of HFMD.
Reporting of scar outcomes in the hand and wrist; a state-of-the-art literature review
Authors: Kennedy Donna L. , Chism-Balangue Tracy , Furniss Dominic
Published: April 2023

Objectives

The aim of this literature review was to synthesise and report current practice in evaluation and reporting of scar outcomes in hand and wrist clinical research.

Methods

A systematic search from inception to 2022 was conducted using three electronic databases. English language randomized controlled trials and observational cohort studies reporting standardised scar outcome measures and/or scar symptoms, appearance, impairment, function, or mental health outcomes in patients with hand and wrist scars were included. Two independent reviewers determined study eligibility and performed data extraction of a priori identified scar outcome domains. Data analysis included descriptive statistics and identification of discordance in taxonomy.

Results

Fifty-nine studies were included. Elective surgery cohorts were the most frequently included clinical population (n = 28; 47%) followed by burns (n = 16; 27%). Six different standardised scar outcome measures were reported by 25% of studies however only 7% of studies utilised a patient-reported measure. Scar symptoms were the most frequently reported outcome domain (81%); but taxonomy was incongruous, constructs lacked working definitions required for generalisability and outcome measurement was variable and unreported. Nineteen different measures of scar appearance and structure were reported by 30 (51%) of studies however only nine (23%) were patient-reported. Seven different hand function PROMs were reported by 25 (43%) studies. Person-centred domains including scar acceptability (12%), mental health impact (5%), and social participation (4%) were rarely reported.

Conclusions

This review highlights that evaluation and reporting of hand and wrist scar outcomes is not standardised, assessment methods and measures are under-reported and there is discordance in taxonomy. Evaluation is not person-centred, rather it is dependent on clinician assessment. Domains including scar acceptability, mental health, and social participation are rarely addressed. A stakeholder consensus derived hand and wrist scar core outcome measurement set will promote standardisation and underpin improvements in clinical research quality, transparency, and rigour.
Outcomes of fixation of Vancouver B periprosthetic fractures around cemented versus uncemented stems
Authors: Barghi Ameen , Hanna Philip , Merchan Nelson , Weaver Michael J. , Wixted John , Appleton Paul , Rodriguez Edward
Published: April 2023

Background

The incidence of periprosthetic femur fracture (PPFF) in the setting of total hip arthroplasty (THA) is steadily increasing. We seek to address whether there is a difference in outcomes between Vancouver B fracture types managed with ORIF when the original stem was a press-fit stem versus a cemented stem.

Methods

In this retrospective cohort study at a level 1 trauma center, we identified 136 patients over 65 years-of-age with Vancouver B-type fractures sustained between 2005 and 2019. Patients were treated by ORIF and had either cemented or press-fit stems prior to their injury. Outcomes were subsidence of the femoral implant, time to full weight bearing, rate of the hip implant revision, estimated blood loss (EBL), postoperative complications, and the one-year mortality rate.

Results

A total of 103 (75.7%) press-fit and 33 (24.3%) cemented patients were reviewed. Patient baseline characteristics, Vancouver fracture sub-types, and implant characteristics were not found to be significantly different between groups. The difference in subsidence rates, postoperative complications, and time to weight bearing were not significantly different between groups. EBL and one-year mortality rate were significantly higher in the cemented group.

Conclusions

In geriatric patients with Vancouver B type periprosthetic fractures managed with ORIF, patients with an originally press fit stem may have lower mortality, lower estimated blood loss, and similar subsidence and hospital length of stays when compared to those with a cemented stem.