bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-population generalizability of a deep learning-based chest radiograph severity score for COVID-19
Authors: Li Matthew D. , Arun Nishanth T. , Aggarwal Mehak , Gupta Sharut , Singh Praveer , Little Brent P. , Mendoza Dexter P. , Corradi Gustavo C.A. , Takahashi Marcelo S. , Ferraciolli Suely F. , Succi Marc D. , Lang Min , Bizzo Bernardo C. , Dayan Ittai , Kitamura Felipe C. , Kalpathy-Cramer Jayashree
Published: July 2022

To tune and test the generalizability of a deep learning-based model for assessment of COVID-19 lung disease severity on chest radiographs (CXRs) from different patient populations.

A published convolutional Siamese neural network-based model previously trained on hospitalized patients with COVID-19 was tuned using 250 outpatient CXRs. This model produces a quantitative measure of COVID-19 lung disease severity (pulmonary x-ray severity (PXS) score). The model was evaluated on CXRs from 4 test sets, including 3 from the United States (patients hospitalized at an academic medical center (N = 154), patients hospitalized at a community hospital (N = 113), and outpatients (N = 108)) and 1 from Brazil (patients at an academic medical center emergency department (N = 303)). Radiologists from both countries independently assigned reference standard CXR severity scores, which were correlated with the PXS scores as a measure of model performance (Pearson R). The Uniform Manifold Approximation and Projection (UMAP) technique was used to visualize the neural network results.

Tuning the deep learning model with outpatient data showed high model performance in 2 United States hospitalized patient datasets (R = 0.88 and R = 0.90, compared to baseline R = 0.86). Model performance was similar, though slightly lower, when tested on the United States outpatient and Brazil emergency department datasets (R = 0.86 and R = 0.85, respectively). UMAP showed that the model learned disease severity information that generalized across test sets.

A deep learning model that extracts a COVID-19 severity score on CXRs showed generalizable performance across multiple populations from 2 continents, including outpatients and hospitalized patients.
Posterior scleritis with choroidal detachments and periaortitis associated with IgG4-related disease: A case report
Authors: Mase Yoko , Kubo Akiko , Matsumoto Akane , Masuda Kosuke , Kadoya Masatoshi , Koizumi Kan , Sotozono Chie , Kondo Mineo
Published: July 2022

Background:

IgG4-related diseases (IgG4-RDs) are known to disrupt the functioning of multiple organs and are usually associated with mass lesions. Periaortitis, an inflammation of the adventitia and tissues surrounding the aorta, is an example of an IgG4-RD. In ophthalmology, an enlargement of the lacrimal gland is a well-known IgG4-RD, and scleritis has also been reported to be an IgG4-RD although it is rare. We report our findings in a case with periaortitis and posterior scleritis that were present at the same time, and they responded well to systemic steroid therapy.

Patients concerns:

A 79-year-old man with dementia and Lewy bodies was referred to our hospital because of uveitis in both eyes that did not respond to topical steroid therapy.

Diagnosis:

We found anterior scleritis in the right eye and uveitis with shallow anterior chambers in both eyes. B-mode echography showed choroidal detachments (CDs) and a T sign in the right eye. The CDs were assumed to have progressed to the posterior scleritis which then caused the severe vision reduction. The patient was referred to the Internal Medicine Department because the systemic inflammatory disease was suspected due to the high levels of C-reactive protein (CRP) and the fast erythrocyte sedimentation rate. Systemic CT scans showed periaortitis only at the lumbar region. Because of the high levels of IgG4, the patient was diagnosed with IgG4-RD.

Interventions:

The patient received intravenous and oral steroid therapy. The first 125 mg of methylprednisolone (mPSL) for 3 days was intravenous, after which it was switched to oral prednisolone (PSL) therapy and the dosage was gradually reduced.

Outcomes:

The posterior scleritis and periaortitis responded well to the systemic steroid therapy. One year and a half after the onset of the disease, the patient is still taking 5 mg of PSL.

Conclusions:

Scleritis with multiple CDs and periaortitis were strongly suspected to be due to IgG4-RD although no definitive diagnosis was made by biopsy of the lesions. Clinicians should be aware that IgG4-RD should be considered as one of the causes of posterior scleritis.
Hemolytic anemia caused by an excessively kinked prosthetic graft after total arch replacement detected by 4-dimensional flow magnetic resonance imaging: A case report
Authors: Takei Yusuke , Shibasaki Ikuko , Suzuki Kohei , Miyazaki Shohei , Hirota Shotaro , Ohashi Hirotaka , Saito Shunsuke , Fukuda Hirotsugu
Published: July 2022

Rationale:

Hemolytic anemia is a rare postoperative complication of aortic surgery, which may be caused by an excessively kinked graft that causes abnormal blood flow. It has been reported that 4-dimensional flow magnetic resonance imaging (4D flow MRI) can identify abnormal flow. Herein, we report the guidance of 4D flow MRI in performing the revision procedure for a patient with hemolytic anemia by evaluating abnormal blood flow based on this method.

Patient concerns:

A 70-year-old woman presented with dizziness and fatigue. She had undergone total arch replacement with a frozen elephant trunk 5 years prior. We diagnosed hemolytic anemia caused by a kinked graft after total arch replacement.

Diagnosis:

Although computed tomography findings revealed 3 lesions of the kinked graft at the ascending portion and cervical branches, 4D flow MRI findings showed that only the kinked graft at the ascending portion caused hemolytic anemia due to an elevated viscous energy loss around it.

Intervention:

We performed surgery to remove the kinked section instead of revision surgery consisting of total arch replacement.

Outcomes:

The patient’s postoperative course was uneventful and there were no complications. Postoperative enhanced computed tomography findings showed that the repaired graft had an adequate length and smoothly curved shape. The 4D flow MRI findings revealed smooth flow in the ascending portion and decreased viscous energy loss.

Lessons:

Based on the 4D flow MRI findings, we adopted a less invasive approach, repairing only the ascending portion of the graft, instead of performing revision surgery comprising total arch replacement.
Protein-bound polysaccharide K prolonged overall survival in gastric cancer patients from a non-Japanese Asian country who received gastrectomy and adjuvant chemotherapy
Authors: Wang Ting-Yao , Chen Chao-Yu , Huang Tzu-Hao , Yang Yao-Hsu , Chen Ko-Jung , Chou Wen-Chi , Lu Chang-Hsien
Published: July 2022

Adding protein-bound polysaccharide K (PSK) to adjuvant chemotherapy with mitomycin and fluorouracil after gastrectomy for gastric cancer was demonstrated to improve survival in a previous study in Japan. However, the efficacy of PSK outside Japan and in combination with other adjuvant chemotherapeutic agents remains unclear. The aims of this study were to evaluate the efficacy of PSK.

We conducted a population-based historical cohort study using the National Health Insurance Research Database of Taiwan. We performed sensitivity analysis with propensity score matching to control for possible confounders. Patients who used PSK (PSK group) were matched at a 1:4 ratio to those who had never used PSK (control group) after adjusting for covariates including sex, age, urbanization, income and comorbidities. The primary outcome was overall survival. Multivariate hazard ratios from competing risk analysis were calculated by adjusting for demographic data and all confounding factors.

From 1999 to 2008, we identified 10,617 patients with gastric cancer received gastrectomy and adjuvant chemotherapy. 1295 patients used PSK (PSK group) and 5180 patients never used PSK (control group) were analyzed after propensity score matching. The median overall survival was 6.49 years (95% confidence interval [CI] 5.22–7.63) in the PSK group and 3.59 years (95% CI 3.38–3.80) in the control group. After adjusting for age, sex, urbanization, income, and comorbidities, adding PSK to adjuvant chemotherapy was the most significant prognostic factor for improved survival (hazard ratio 0.76, P < .0001).

Adjuvant chemotherapy combined with PSK significantly prolonged overall survival in gastric cancer patients after gastrectomy.
Clinical and histopathological analyses of kidney biopsies in a single center for 7 years
Authors: Lee Seunghye , Jung Sehyun , Kim Mi-Ji , Lee Jong Sil , Jang Ha Nee , Chang Se-Ho , Kim Hyun-Jung
Published: July 2022

Kidney biopsy is the most important tool for diagnosing kidney disease and can be helpful in determining treatment and prognosis. Pathological spectra vary by country, region, race, sex, and age. We are the first to investigate the pathological spectrum of biopsy-proven kidney disease in Gyeongnam province of South Korea. We retrospectively analyzed 631 patients who underwent a kidney biopsy between 2013 and 2019 at Gyeongsang National University Hospital. The mean age of the 631 patients was 51.5 ± 18.1 years, and 361 patients (57.2%) were male. The mean estimated glomerular filtration rate by serum creatinine (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) was 68.0 ± 45.7 mL/min/1.73 m2. The mean systolic blood pressure was higher in 2017, 2018, and 2019 than in 2013 (P = .002). Hypertension (47.4%) was the most common comorbid disease, followed by diabetes (18.2%) and dyslipidemia (10.9%). Common clinical syndromes at the time of biopsy were renal insufficiency (42.0%) and nephrotic syndrome (33.9%). The prevalence of primary and secondary glomerular disease and tubulointerstitial disease were 71.4%, 16.9%, and 5.4%, respectively. Immunoglobulin A nephropathy was the most common primary glomerular disease (34.9%). Diabetic nephropathy was the most common secondary glomerular disease, followed by lupus nephritis. Tubulointerstitial disease was underestimated, as in other reports. Our data can be a useful reference for diagnosing kidney disease and understanding the patients in our province.
Long-term impact of certain coexisting extrahepatic unisystem and multisystem manifestations on trends in incidence of liver cirrhosis in treatment-naïve patients with chronic hepatitis C: A nested case-control study
Authors: Wang Chun-Hsiang , Ou Shih-Fang , Tseng Yuan-Tsung
Published: July 2022

Diabetes mellitus (DM) was found to be more common in hepatitis C virus (HCV)-related cirrhotic males. However, the association between DM, or other extrahepatic manifestations (EHMs), and liver cirrhosis is still undetermined. We used a large-scale long-term study to analyze the cirrhosis risk of treatment-naïve HCV patients with EHMs as compared to those without.

In this retrospective nested case-control study, we identified 11 872 treatment-naïve patients with chronic HCV between 2001 and 2013 from Taiwan National Health Insurance Research Database and divided them into patients with (cases) and without cirrhosis (controls). All patients were followed up from the index month (exact month of diagnosis) to the end of 2013, death, or study outcome, whichever occurred first. The cases and controls were 1:6 propensity score matched for age, sex, and exact month of diagnosis; finally, 8078 patients (1154 with and 6924 without cirrhosis) were included in the analysis. The presence of coexisting EHMs and a new diagnosis of cirrhosis was analyzed. Adjusted hazard ratios (HRs) and cumulative incidence for cirrhosis were calculated in conditional Cox regression models after propensity score matching.

Patients with high-cirrhosis-risk EHMs, such as DM (HR: 1.72, 95% CI: 1.51–1.96, P < .001), HCD (HR: 1.45, 95% CI: 1.27–1.67, P < .007), CKD (HR: 1.21, 95% CI: 1.05–1.38, P < .001), hyperlipidemia (HR: 0.53, 95% CI: 0.46–0.60, P < .001), lichen planus (HR: 2.71, 95% CI: 1.56–4.72, P < .001), and palpable purpura (HR: 2.67, 95% CI: 2.13–3.35, P < .001) exhibited significantly higher risk of liver cirrhosis than those without. Cumulative incidence (P < .001) of liver cirrhosis by pairwise comparisons of multiple high-cirrhosis-risk EHMs, and that of lichen planus was the highest.

Our study provided direct estimates of specific HCV-associated EHM time trends of cirrhosis risk, with an upward trend in incidence. Lichen planus was at the top of the list of single-EHM comparisons, and the maximum combination of certain EHMs was the greatest risk factor across a different array of multi-EHM comparisons for liver cirrhosis development.
Association of AGTR1 gene methylation and its genetic variant in Chinese farmer with hypertension: A case-control study
Authors: Li Zhi-yuan , Ma Qiang , Li Xing , Yu Shui-yuan , Zuo Juan , Wang Chong-jian , Li Wen-jie , Ba Yue , Yu Fang-fang
Published: July 2022

The objective was to determine the potential associations of the angiotensin II receptor type 1 (AGTR1) gene polymorphism, methylation, and lipid metabolism in Chinese farmers with hypertension.

A case-control study was conducted in Wuzhi county of Henan province in China in 2013 to 2014. A total of 1034 local residents (35–74 years, 386 hypertensive cases, and 648 normotensive subjects) were enrolled in this study. Triglyceride (TG), total cholesterol (TC), high-density lipoprotein, and low-density lipoprotein were measured using automatic chemistry analyzer. The AGTR1 gene promoter methylation level was measured using quantitative methylation-specific polymerase chain reaction method. The single nucleotide polymorphism rs275653 was genotyped with TaqMan probe assay at an applied biosystems platform.

The gender, body mass index (BMI), TG, TC, and family history of hypertension in the hypertension group were significantly higher than those in control group (P < .05). No significant difference was observed in the distribution of AGTR1 rs275653 polymorphism in the hypertension and controls (P > .05). The AGTR1 gene methylation in subjects carrying different genotypes was not significantly observed (P > .05). The logistic regression analysis found the AGTR1 gene methylation level was negative correlation with hypertension in the present study (odds ratio, 0.946, 95% confidence interval, 0.896–0.999) through adjusting for age, gender, BMI, education, smoking, alcohol drinking, fruit and vegetable intake, pickles intake, and family history of hypertension.

The association of AGTR1 gene hypomethylation and essential hypertension was observed in Chinese farmers; no significant difference was observed in the distribution of AGTR1 rs275653 polymorphism.
Malignant testicular tumors in children: A single institution’s 12-year experience
Authors: Chiu Chia-Chi , Jaing Tang-Her , Lai Jin-Yao , Chen Shih-Hsiang , Chang Tsung-Yen , Hsueh Chuen , Wen Yu-Chuan , Tsay Pei-Kwei
Published: July 2022

Testicular neoplasms are not commonly found in children and are a formidable threat if treated inappropriately. However, there is no consensus regarding its management. This study aimed to create a holistic picture of the interprofessional team in the management of malignant testicular tumors.

Seventeen patients had mixed germ cell tumors, 15 had pure yolk sac tumors, 2 had immature teratomas, 2 had teratocarcinomas, and 1 had a sex cord stromal tumor. Five lesions were diagnosed as nongerm cell tumors: 2 embryonal rhabdomyosarcomas, 2 lymphomas, and 1 acute myeloid leukemia. At initial presentation, retroperitoneal (n = 2), bone marrow (n =1), and mediastinal (n = 1) metastases were identified in 4 (10%) patients. The operative interventions performed included radical inguinal orchiectomy (n = 5), scrotal orchiectomy (n = 31), and testicular biopsy or testis-sparing enucleation of the tumor (n = 6). Postoperatively, 18 patients received either adjuvant chemotherapy (n = 14) or chemoradiation (n = 5). Five patients with mixed germ cell tumors (n = 2), group IV paratesticular rhabdomyosarcoma (n = 2), and acute myeloid leukemia with myeloid sarcoma (n =1) died of disease progression. Thirty-six patients remained alive and disease-free at the last visit.

Malignant testicular tumors in children deserve proper diagnostic support from a therapeutic perspective. Any concern or suspicion of a testicular tumor warrants an inguinal approach to avoid scrotal violation.
Comparison of pain and psychosocial correlates among Hispanic and Non-Hispanic White youth with chronic pain
Authors: Goya Arce Ana B. , Richardson Patricia A. , Tran Susan T. , Bhandari Rashmi P.
Published: July 2022

Introduction:

Despite well-documented pain disparities among adults from non-White and Hispanic groups, less is known about pain disparities in non-White and Hispanic pediatric populations.

Objectives:

We compare pain and related psychosocial factors at the individual (pain intensity, pain interference, pain catastrophizing, co-occurring symptoms), social (peer relations), and systemic (health insurance) levels among Hispanic and Non-Hispanic White (NHW) youth with chronic pain.

Methods:

Eight hundred thirty-seven (71.4% female) Hispanic (n = 268, 32%) and NHW (n = 569, 68%) youth ages 8 to 17 years (M = 14.00; SD = 2.54) completed a survey at their initial visit to a pain clinic. Independent sample t tests investigated mean differences in psychosocial factors at the individual and social levels. Chi-squared tests investigated differences at the systemic level. Bivariate correlations for each group were compared using Fisher r-to-z transformations.

Results:.

Hispanic youth reported higher levels of pain intensity (t[811] = −2.75, P = 0.006). Groups did not differ in reports of other individual or social factors. Non-Hispanic White youth were more likely to have private insurance (OR, 5.66). All examined variables were significantly correlated among NHW youth. Correlations were weaker or nonsignificant among Hispanic youth. Fisher r-to-z transformations revealed these group differences to be significant.

Conclusion:

Hispanic youth report higher pain levels than NHW counterparts and lower likelihood of having private insurance. Pain and psychosocial factors correlate differently among the 2 groups highlighting a need to better understand the chronic pain experiences of diverse youth because models derived primarily from NHW populations may not generalize across ethnic and racial groups.
Antiretroviral therapy initiation within 7 and 8–30 days post-HIV diagnosis demonstrates similar benefits in resource-limited settings
Authors: Zhao Bin , Ding Haibo , Song Wei , Kang Mingming , Dong Xue , Li Xin , Wang Lu , Liu Jianmin , Chu Zhenxing , Wang Lin , Tian Wen , Qiu Yu , Shang Hong , Han Xiaoxu
Published: July 2022

We estimated the optimum time to initiate antiretroviral therapy (ART) in a retrospective observational cohort. We observed that ART initiation 7 days or less (n = 817) and 8–30 days (n = 1009) were the most important factors with viral suppression, and had similar viral suppression rate, CD4+ T-cell count increase and fractions of individuals with links at least 4 and individuals linked to recent HIV infection in HIV molecular networks. This study provides real-world evidence on the benefits of rapid ART initiation in resource-limited setting.
11C-Acetate PET/CT Detects Reactive Astrogliosis Helping Glioma Classification
Authors: Kim Dongwoo , Chun Joong Hyun , Yi Ju Hyeon , Ko Hae Young , Chung Jee-In , Lee Misu , Park Yongmin Mason , Nam Min-Ho , Kim Jisu , Kim Seon Yoo , Park Youngjoo , Moon Ju Hyung , Kang Seok-Gu , Chang Jong Hee , Lee C. Justin , Kim Se Hoon , Yun Mijin
Published: July 2022

Purpose

11C-acetate (11C-ACE) uptake on PET/CT was recently discovered to represent reactive astrocytes in the tumor microenvironment. This study aimed at evaluating the role of 11C-ACE PET/CT as an imaging biomarker of reactive astrogliosis in characterizing different types of gliomas.

Methods

In this prospective study, a total of 182 patients underwent 11C-ACE PET/CT before surgery. The ratio of SUVmax of a glioma to the SUVmean of the contralateral choroid plexus (11C-ACE TCR) on PET/CT was calculated. 11C-ACE TCRs were compared with the World Health Organization grades and isocitrate dehydrogenase 1 (IDH1) mutation status. Grade 2 was considered low-grade tumor, and grades 3 and 4 were considered high-grade tumors.

Results

The median 11C-ACE TCR was significantly higher in IDH1 wild-type (wt) tumors (n = 91) than in IDH1-mutant (mt) tumors (n = 91) (2.38 vs 1.30, P < 0.001). Of the 91 IDH1-mt tumors, there were no differences in the median 11C-ACE TCRs between oligodendrogliomas (ODs) and astrocytic tumors (1.40 vs 1.20, P > 0.05). In grading low- versus high-grade gliomas, the receiver operating characteristic curve analyses showed a higher area under the curve (0.951) in IDH1-wt tumors than in IDH1-mt tumors (0.783, P = 0.002). Grade 2 ODs were well differentiated from high-grade gliomas. The 11C-ACE TCR of grade 3 ODs was significantly lower than that of IDH1-wt glioblastomas.

Conclusions

High 11C-ACE uptake is associated with high-grade IDH1-wt tumors, thus facilitating differentiation from high-grade IDH1-mt and low-grade gliomas. In particular, low 11C-ACE uptake in ODs is advantageous in overcoming the limitation of radiolabeled amino acid tracers.
Serous Cystadenoma of the Pancreas Showing Increased Uptake on 68Ga-FAPI PET/CT
Authors: Xu Weizhi , Zhao Long , Meng Tinghua , Shang Qihang , Chen Haojun
Published: July 2022

Serous cystadenoma of the pancreas is a type of pancreatic cystic neoplasm frequently found in clinical practice. Serous cystadenoma of the pancreas can have a varied morphological presentation on imaging examinations. Therefore, it is sometimes very challenging to differentiate serous cystadenoma of the pancreas from pancreatic malignancy. In this study, we present a case of serous cystadenoma of the pancreas showing focally elevated radiotracer uptake on 68Ga-FAPI PET/CT. Considering potential future clinical use of 68Ga-FAPI PET/CT in malignancy, awareness of the false-positive findings is important for the differential diagnosis and management of these lesions.
A Preliminary Study of a Novel Reference Plane of the Head: Comparing With the True Horizontal Plane
Authors: Tian Kaiyue , Zhou Zuo , Zhang Kaiyu , Wang Lin
Published: July 2022

A new reference plane of the head, based on soft tissue landmarks and suitable for clinical analysis and soft tissue measurements, is needed. We recently discovered a novel reference plane, that is, the COs plane, which was formed by bilateral Lateral Canthus and bilateral Otobasion Superius and might be horizontal at the natural head position (NHP). In this study, we investigated the angles between the COs plane and the true horizontal (TrH) plane while sitting and standing, aiming to explore whether the new plane could be used as a substitution for the reference plane in clinical practice. Briefly, 26 volunteers were enrolled. Their sitting and standing NHP were recorded using the 3dMDface system. In the pitch axis, the mean angle of COs/TrH was 0.29 degrees and 0.41 degrees for sitting and standing positions, respectively, showing no statistical difference (P>0.05). However, in the roll axis, the mean angle of COs/TrH for sitting position and standing positions was 1.08 and 1.33 degrees (P<0.05), which was considered to be the result of habitual canting of the head. Moreover, there were no significant differences between the sitting and standing NHP, considering the COs/TrH angles (P>0.05). To sum up, we concluded that the COs plane could be used as a reliable reference plane in certain soft tissue analysis and clinical applications.
Machine Learning Risk Prediction Model of 90-day Mortality After Gastrectomy for Cancer
Authors: Pera Manuel , Gibert Joan , Gimeno Marta , Garsot Elisenda , Eizaguirre Emma , Miró Mónica , Castro Sandra , Miranda Coro , Reka Lorena , Leturio Saioa , González-Duaigües Marta , Codony Clara , Gobbini Yanina , Luna Alexis , Fernández–Ananín Sonia , Sarriugarte Aingeru , Olona Carles , Rodríguez-Santiago Joaquín , Osorio Javier , Grande Luis ,   on behalf of the Spanish EURECCA Esophagogastric Cancer Group
Published: July 2022

Objective:

To develop and validate a risk prediction model of 90-day mortality (90DM) using machine learning in a large multicenter cohort of patients undergoing gastric cancer resection with curative intent.

Background:

The 90DM rate after gastrectomy for cancer is a quality of care indicator in surgical oncology. There is a lack of well-validated instruments for personalized prognosis of gastric cancer.

Methods:

Consecutive patients with gastric adenocarcinoma who underwent potentially curative gastrectomy between 2014 and 2021 registered in the Spanish EURECCA Esophagogastric Cancer Registry database were included. The 90DM for all causes was the study outcome. Preoperative clinical characteristics were tested in four 90DM predictive models: Cross Validated Elastic regularized logistic regression method (cv-Enet), boosting linear regression (glmboost), random forest, and an ensemble model. Performance was evaluated using the area under the curve by 10-fold cross-validation.

Results:

A total of 3182 and 260 patients from 39 institutions in 6 regions were included in the development and validation cohorts, respectively. The 90DM rate was 5.6% and 6.2%, respectively. The random forest model showed the best discrimination capacity with a validated area under the curve of 0.844 [95% confidence interval (CI): 0.841–0.848] as compared with cv-Enet (0.796, 95% CI: 0.784–0.808), glmboost (0.797, 95% CI: 0.785–0.809), and ensemble model (0.847, 95% CI: 0.836–0.858) in the development cohort. Similar discriminative capacity was observed in the validation cohort.

Conclusions:

A robust clinical model for predicting the risk of 90DM after surgery of gastric cancer was developed. Its use may aid patients and surgeons in making informed decisions.
Neck pain care pathways and costs: association with the type of initial contact health care provider. A retrospective cohort study
Authors: Elton David , Zhang Meng
Published: July 2022

Background

For individuals with neck pain (NP) the type of health care provider (HCP) initially contacted and subsequent services used are less well understood than for low back pain (LBP). The purpose of this retrospective observational study of administrative data was to examine the association between type of HCP initially contacted by individuals with NP, service utilization, and total episode cost.

Methods

A US national sample of NP episodes completed in 2017-2019 was analyzed. Separate analyses of a combined surgical and non-surgical (pooled) sample and a non-surgical sample were performed. Seventeen types of HCP initially contacted by an individual with NP was the primary independent variable. Dependent measures included rate and timing of use of fourteen types of health care services and total episode cost. A mixed effects model applied to pooled and non-surgical samples was used to test the association between initial contact HCP, total episode cost and rate of prescription opioid and NSAID use for NP.

Results

The study included 323,348 continuously insured individuals aged 18 years and older with 390,992 complete episodes of NP involving 321,538 HCPs and incurring $472,399,064 in expenditures. 53.0% of episodes had initial contact with a primary care or specialist HCP, with these episodes associated with higher rates of imaging, pharmaceutical, and interventional services. 40.4% of episodes had initial contact with a non-prescribing HCP, with these episodes associated with higher rates of non-pharmaceutical services. Chiropractors (DC) were the most common type of HCP initially contacted (38.5% of episodes) and were associated with the lowest adjusted total episode cost. Results were consistent for individuals experiencing single or multiple episodes during the study period.

Conclusions

This study of a large US cohort of commercially insured individuals with NP helps fill a knowledge gap regarding NP care pathway attributes. Like LBP, the treatment of NP is highly variable with the initial HCP selected by an individual with NP associated with differences in services received and episode cost. Initial contact with a non-prescribing HCP was associated with lower rates of imaging, pharmacology, and interventional services.
Forms of support and experiencing maltreatment and disrespect during childbirth at a health facility: a self-reported cross-sectional study in Ghana
Authors: Asare Agnes , Tabong Philip Teg-Nefaah
Published: July 2022

Providing support to women and encouraging women to deliver in health facility settings (skilled delivery) is one strategy to improve maternal health outcomes in developing countries. However, fear of maltreatment and disrespect during labour and delivery, have been reported as barriers to facility delivery. This study was therefore conducted to assess postnatal women’s self-reported experience and type of maltreatment and disrespect during delivery. Using a cross sectional study design, 313 women were randomly selected from the three health facilities located in the La-Nkwantenang-Madina Municipality in the Greater Accra region. The data was analysed using STATA 15. Bivariable data analysis using Pearson’s Chi-square was used to determine the association between socio-demographic characteristics, reproductive history and experience of maltreatment. Logistic regression analysis was done to determine the strengths of association. More than half (54.3%) of the postnatal women were encouraged to have support persons during labour and delivery. About 75.7% reported experiencing some form of maltreatment and disrespect. About a fifth (19.8%, n=62) of the women experienced physical abuse, 9.3% (n=29) experienced undignified care, 7.7% (n=24) of the women were detained or confined against their will, and 60.4% (n=189) indicated they did not receive consented care. The study concludes that maltreatment and disrespect during labour is widespread. Expanding health facilities may not achieve desired skilled or facility-based delivery without improving the birth experience of women.
CSF metabolites associated with biomarkers of Alzheimer’s disease pathology
Authors: Dong Ruocheng , Lu Qiongshi , Kang Hyunseung , Suridjan Ivonne , Kollmorgen Gwendlyn , Wild Norbert , Deming Yuetiva , Van Hulle Carol A. , Anderson Rozalyn M. , Zetterberg Henrik , Blennow Kaj , Carlsson Cynthia M. , Asthana Sanjay , Johnson Sterling C. , Engelman Corinne D.
Published: July 2022

INTRODUCTION

Metabolomics technology facilitates studying associations between small molecules and disease processes. Correlating metabolites in cerebrospinal fluid (CSF) with Alzheimer’s disease (AD) CSF biomarkers may elucidate additional changes that are associated with early AD pathology and enhance our knowledge of the disease.

METHODS

The relative abundance of untargeted metabolites was assessed in 161 individuals. A metabolome-wide association study (MWAS) was conducted between 269 CSF metabolites and protein biomarkers reflecting brain amyloidosis, tau pathology, neuronal and synaptic degeneration, and astrocyte or microglial activation and neuroinflammation. Linear mixed-effects regression analyses were performed with random intercepts for sample relatedness and repeated measurements and fixed effects for age, sex, and years of education. The metabolome-wide significance was determined by a false discovery rate threshold of 0.05. The significant metabolites were replicated in 154 independent individuals. Mendelian randomization was performed using genome-wide significant single nucleotide polymorphisms from a CSF metabolites genome-wide association study.

RESULTS

MWAS results showed several significantly associated metabolites for all the biomarkers except Aβ42/40 and IL-6. Genetic variants associated with metabolites and Mendelian randomization analysis provided evidence for a causal association of metabolites for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), amyloid β (Aβ40), α-synuclein, total tau, phosphorylated tau, and neurogranin, for example, palmitoyl sphingomyelin (d18:1/16:0) for sTREM2, and erythritol for Aβ40 and α-synuclein.

DISCUSSION

This study provides evidence that CSF metabolites are associated with AD-related pathology, and many of these associations may be causal.
Mendelian randomization confirms the role of Y-chromosome loss in Alzheimer’s Disease etiopathogenesis in males
Authors: García-González Pablo , de Rojas Itziar , Moreno-Grau Sonia , Montrreal Laura , Puerta Raquel , Alarcón-Martín Emilio , Quintela Inés , Orellana Adela , Andrade Victor , Adami Pamela Martino , Heilmann-Heimbach Stefanie , Gomez-Garre Pilar , Teresa Periñán María , Alvarez Ignacio , Diez-Fairen Monica , Nuñez Llaves Raul , Olivé Roig Claudia , Garcia-Ribas Guillermo , Menéndez-González Manuel , Martínez Carmen , Aguilar Miquel , Buongiorno Mariateresa , Franco-Macías Emilio , Saez Maria Eugenia , Cano Amanda , Bullido Maria , Real Luis , Rodríguez-Rodríguez Eloy , Royo Jose , Álvarez Victoria , Pastor Pau , Piñol-Ripoll Gerard , Mir Pablo , Lara Miguel Calero , Padilla Miguel Medina , Sánchez-Juan Pascual , Carracedo Angel , Valero Sergi , Hernandez Isabel , Tàrraga Lluis , Ramirez Alfredo , Boada Mercé , Ruiz Agustín
Published: July 2022

Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event occurring exclusively in men and has been previously associated with Alzheimer’s disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomization to construct an age-independent polygenic risk score of mLOY (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per SD unit (p=4.22·10−20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in males with mild cognitive impairment (HR=1.23; p=0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group. The male-specificity of the observed effects suggests that these associations of mLOY with AD are caused by the inherent loss of the Y chromosome, and not by the increased genomic instability underlying mLOY risk. Additionally, we found that blood mLOY phenotype was associated with increased CSF levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesis. Furthermore, we encourage researchers to use this mloy-PRS instrument to find unbiased associations between mLOY and ageing-related diseases.
Assessing Etiologic Heterogeneity for Multinomial Outcome with Two-Phase Outcome-Dependent Sampling Design
Authors: Reifeis Sarah A. , Hudgens Michael G. , Troester Melissa A. , Love Michael I.
Published: July 2022

Etiologic heterogeneity occurs when distinct sets of events or exposures give rise to different subtypes of disease. Inference about subtype-specific exposure effects from two-phase outcome-dependent sampling data requires adjustment for both confounding and the sampling design. Common approaches to inference for these effects do not necessarily appropriately adjust for these sources of bias, or allow for formal comparisons of effects across different subtypes. Herein, using inverse probability weighting (IPW) to fit a multinomial model is shown to yield valid inference with this sampling design for subtype-specific exposure effects and contrasts thereof. The IPW approach is compared to common regression-based methods for assessing exposure effect heterogeneity using simulations. The methods are applied to estimate subtype-specific effects of various exposures on breast cancer risk in the Carolina Breast Cancer Study.
Changes in mobility patterns during the COVID-19 pandemic in Zambia: implications for the effectiveness of NPIs in Sub-Saharan Africa
Authors: Loisate Stacie , Mutembo Simon , Arambepola Rohan , Makungo Kabondo , Kabalo Elliot N , Sinyange Nyambe B. , Kapata Nathan , Liwewe Mazyanga , Silumezi Andrew , Chongwe Gershom , Kostandova Natalya , Truelove Shaun , Wesolowski Amy
Published: July 2022

The COVID-19 pandemic has impacted many facets of human behavior, including human mobility partially driven by the implementation of non-pharmaceutical interventions (NPIs) such as stay at home orders, travel restrictions, and workplace and school closures. Given the importance of human mobility in the transmission of SARS-CoV-2, there have been an increase in analyses of mobility data to understand the COVID-19 pandemic to date. However, despite an abundance of these analyses, few have focused on Sub-Saharan Africa (SSA). Here, we use mobile phone calling data to provide a spatially refined analysis of sub-national human mobility patterns during the COVID-19 pandemic from March 2020-July 2021 in Zambia. Overall, among highly trafficked intra-province routes, mobility decreased up to 52% from March-May 2020 compared to baseline, which was also the time period of the strictest NPIs. However, despite dips in mobility during the first wave of COVID-19 cases, mobility returned to baseline levels and did not drop again suggesting COVID-19 cases did not influence mobility in subsequent waves.
Characterization and Preclinical Treatment of Rotational Force-Induced Brain Injury
Authors: Umfress Alan , Chakraborti Ayanabha , Sudarsana Devi Suma Priya , Adams Raegan , Epstein Daniel , Massicano Adriana , Sorace Anna , Singh Sarbjit , Hossian M. Iqbal , Andrabi Shaida A. , Crossman David K. , Kumar Nilesh , Mukhtar M. Shahid , Simpson Claire , Abell Kathryn , Stokes Matthew , Wiederhold Thorsten , Rosen Charles , Luo Huiyang , Lu Hongbing , Natarajan Amarnath , Bibb James A.
Published: July 2022

Millions of traumatic brain injuries (TBIs) occur annually. TBIs commonly result from falls, traffic accidents, and sports-related injuries, all of which involve rotational acceleration/deceleration of the brain. During these injuries, the brain endures a multitude of primary insults including compression of brain tissue, damaged vasculature, and diffuse axonal injury. All of these deleterious effects can contribute to secondary brain ischemia, cellular death, and neuroinflammation that progress for weeks to months after injury and impede neurological recovery. While the linear effects of head trauma have been extensively modeled, less is known about how rotational injuries mediate neuronal damage following injury. Here, we developed a new model of rotational head trauma in rodents and extensively characterized the pathological, behavioral, and electrophysiological effects of rotational TBI (rTBI). We identify aberrant cyclin dependent kinase 5 (Cdk5) activity as a principal mediator of rTBI and show pharmacological inhibition of Cdk5 reduces the cognitive and pathological consequences of injury. Finally, we utilize Cdk5-enriched phosphoproteomics to uncover potential downstream mediators of rTBI. These studies contribute meaningfully to our understanding of the mechanisms of rTBI and how they may be effectively treated.
Sensitive and Selective Polymer Condensation at Membrane Surface Driven by Positive Co-operativity
Authors: Liu Zhuang , Yethiraj Arun , Cui Qiang
Published: July 2022

Biomolecular phase separation has emerged as an essential mechanism for cellular organization. How cells respond to environmental stimuli in a robust and sensitive manner to build functional condensates at the proper time and location is only starting to be understood. Recently, lipid membranes have been recognized as an important regulatory center for biomolecular condensation. However, how the interplay between the phase behaviors of cellular membranes and surface biopolymers may contribute to the regulation of surface condensation remains to be elucidated. Using simulations and a mean-field theoretical model, we show that two key factors are the membrane’s tendency to phase separate and the surface polymer’s ability to reorganize local membrane composition. Surface condensate forms with high sensitivity and selectivity in response to features of biopolymer when positive co-operativity is established between coupled growth of the condensate and local lipid domains. This effect relating the degree of membrane-surface polymer co-operativity and condensate property regulation is shown to be robust by different ways of tuning the co-operativity, such as varying membrane protein obstacle concentration, lipid composition and the affinity between lipid and polymer. The general physical principle emerged from the current analysis may have implications in other biological processes and beyond.
Exploring Phylogenetic Classification and Further Applications of Codon Usage Frequencies
Authors: Hallee Logan
Published: July 2022

Codons are the repeats of three nucleic acids in genetic material read during translation. 64 total codons exist at different frequencies known to vary between organisms. Codon usage frequencies (CUFs) have recently been used for phylogenetic classification at different discrimination levels. However, the accuracy of phylogenetic classification and applications of this predictive power are not fully elucidated in the current literature. The goal of this project was two-fold: 1.) To increase the accuracy and depth of phylogenetic classification models using CUFs in literature. 2.) To explore the potential application of identifying open reading frames (ORFs) with CUFs. To increase the accuracy of classification models GridSearchCV, TensorFlow, and keras were used to design an improved Artificial Neural Network than the relevant example in the literature. Commonly used predictors were explored in an ensemble format that performs even better than the improved neural network. To explore a more discriminatory and phylogenetically deep classification K Means was used to look at possible clustering structures in the CUF data. To identify ORFs the codon frequencies of each potential ORF are compared to the frequencies of an organism of choice with a multinomial goodness-of-fit test. With correct optimization, these tests can reject possible ORFs with high confidence. In addition to these goals, the codons were ranked in terms of importance for classification with lasso regression and random forests feature ranking. This not only highlights exciting biology related to tRNA concentrations and the variance thereof, but is also helpful for optimizing the statistical tests for ORF identification.
Assessing extracellular vesicles in human biofluids using flow-based analyzers
Authors: Krzyzaniak Olga , Wai Yim Kevin Ho , Al Hrout Ala’a , Peacock Ben , Chahwan Richard
Published: July 2022

Extracellular vesicles (EVs) are increasingly being analyzed by flow cytometry. Yet, their miniscule size and low refractive index, causes the scatter intensity of most EVs to fall below the detection limit of most flow cytometers. A new class of devices, known as spectral flow analyzers, are becoming standards in cell phenotyping studies. Largely, due to their unique capacity of detecting a vast panel of markers with higher sensitivity for light scatter detection. Another class of devices, known as nano-analyzers, provides high resolution detection of sub-micron sized particles. Here, we aim to compare the EVs phenotyping performance between the Aurora (Cytek) spectral cell analyzer and the NanoFCM (nFCM) nanoflow analyzer. These two devices were specifically chosen given their lead in becoming gold standards in their respective fields. Immune cell-derived EVs remain poorly characterized despite their clinical potentials. We therefore, used B- and T- cell line-derived EVs and donor-matched human biofluid-derived EVs from serum, urine, and saliva in combination with a panel of established immune markers for this comparative study. A comparative evaluation of both cytometry platforms was performed, discussing their potential and suitability for different applications. We found that nFCM can accurately i) analyze small EVs (40 to 200 nm) matching the size accuracy of electron microscopy; ii) measure concentration of single EV particle per volume; iii) identify underrepresented EV marker subsets; and iv) provide co-localization of EV surface markers. We could also show that human sample biofluids have unique EV marker signatures that could have future clinical relevance.
Incorporating Prior Genomic Dose-Response Data to Support the Benchmark Dose Estimation of Toxicogenomics
Authors: Ji Chao , Shao Kan
Published: July 2022

Chemical risk assessment is an important tool to evaluate the toxicity of chemicals in the environment, and high throughput toxicogenomics plays an increasingly important role in risk assessment. In toxicogenomics, dose-response analysis for each gene is a data-limited situation, and thus parameter and benchmark dose (BMD) estimations typically have large uncertainty. To solve this problem, an informative prior by synthesizing toxicological information is integrated into the Bayesian benchmark dose modeling system (BBMD), a leading web-based toxicogenomics analysis application. We analyzed 276,126 toxicogenomics dose-response datasets and obtained plausible estimation of informative priors for seven commonly used continuous dose-response models. The effects of informative priors are investigated at the individual probe and pathway levels. Simulation studies based on six “true” models generated from typical genomic dose-response shapes show a significant decrease in uncertainty and an increase in accuracy of BMD estimates for most scenarios with informative priors than the counterpart with uninformative priors. The case study on the pathway analysis indicates that informative priors slightly improve the correlation between the pathway-based point of departure and apical point of departure. Overall, our study provides a practical strategy to incorporate existing toxicogenomic information as priors to improve the quality of chemical risk assessment.

Graphic abstract