bluuebunny/crossref_metadata_2025_split huggingface dataset:
On Information Rank Deficiency in Phenotypic Covariance Matrices
Authors: O’Keefe F Robin , Meachen Julie A , Polly P David 
Published: October 2021

AbstractThis article investigates a form of rank deficiency in phenotypic covariance matrices derived from geometric morphometric data, and its impact on measures of phenotypic integration. We first define a type of rank deficiency based on information theory then demonstrate that this deficiency impairs the performance of phenotypic integration metrics in a model system. Lastly, we propose methods to treat for this information rank deficiency. Our first goal is to establish how the rank of a typical geometric morphometric covariance matrix relates to the information entropy of its eigenvalue spectrum. This requires clear definitions of matrix rank, of which we define three: the full matrix rank (equal to the number of input variables), the mathematical rank (the number of nonzero eigenvalues), and the information rank or “effective rank” (equal to the number of nonredundant eigenvalues). We demonstrate that effective rank deficiency arises from a combination of methodological factors—Generalized Procrustes analysis, use of the correlation matrix, and insufficient sample size—as well as phenotypic covariance. Secondly, we use dire wolf jaws to document how differences in effective rank deficiency bias two metrics used to measure phenotypic integration. The eigenvalue variance characterizes the integration change incorrectly, and the standardized generalized variance lacks the sensitivity needed to detect subtle changes in integration. Both metrics are impacted by the inclusion of many small, but nonzero, eigenvalues arising from a lack of information in the covariance matrix, a problem that usually becomes more pronounced as the number of landmarks increases. We propose a new metric for phenotypic integration that combines the standardized generalized variance with information entropy. This metric is equivalent to the standardized generalized variance but calculated only from those eigenvalues that carry nonredundant information. It is the standardized generalized variance scaled to the effective rank of the eigenvalue spectrum. We demonstrate that this metric successfully detects the shift of integration in our dire wolf sample. Our third goal is to generalize the new metric to compare data sets with different sample sizes and numbers of variables. We develop a standardization for matrix information based on data permutation then demonstrate that Smilodon jaws are more integrated than dire wolf jaws. Finally, we describe how our information entropy-based measure allows phenotypic integration to be compared in dense semilandmark data sets without bias, allowing characterization of the information content of any given shape, a quantity we term “latent dispersion”. [Canis dirus; Dire wolf; effective dispersion; effective rank; geometric morphometrics; information entropy; latent dispersion; modularity and integration; phenotypic integration; relative dispersion.]
Revisiting the X:BOT Naltrexone Clinical Trial Using a Comprehensive Survival Analysis
Authors: Ajazi Elizabeth M. , Dasgupta Nabarun , Marshall Stephen W. , Monaco Jane , Howard Annie Green , Preisser John S. , Schwartz Todd A. 
Published: October 2021

Objectives
This paper illustrates survival models for analysis of trials of substance use treatment programs. It uses public release data from a study of extended-release naltrexone (XR-NTX), relative to buprenorphine-naloxone (BUP-NX).

Methods
We used publicly available data from the X:BOT trial (n = 570), which compared XR-NTX to BUP-NX on 2 efficacy outcomes (opioid relapse, use of nonprescribed opioids; positive opioid urine test) and 1 safety outcome (overdose). Intention-to-treat (ITT) and per-protocol approaches were implemented using survival models that included treatment-by-time interactions.

Results
Consistent with the original trial findings, 72% of XR-NTX and 94% of BUP-NX subjects initiated treatment; the ITT hazard ratio for XR-NTX relative to BUP-NX was 1.40 (95% confidence interval: 1.13, 1.73; P < 0.01) for opioid relapse and 1.31 (1.07, 1.60; P = 0.01) for positive urine test. Using treatment-by-time interactions, we examined the time-dependent effect of XR-NTX and found an elevated ITT overdose hazard ratio of 2.4 (1.1, 5.3; P = 0.03) overall and 3.8 (1.2, 11.6; P = 0.02) during the study treatment phase. This result (28 overdoses overall; 17 overdoses during the study treatment phase) contrasts with the previous analysis, which reported minimal differences in overdose between XR-NTX and BUP-NX.

Conclusions
An advantage of using time-dependent Cox models is its ability to isolate effects during specific periods. In general, our survival analyses concur with the conclusions of Lee et al (2018) for the efficacy outcomes, which demonstrated superiority of BUP-NX. In contrast to the original report, our analysis indicates a greater risk of overdose for XR-NTX, predominantly during the study treatment phase. Further investigation of this finding is a pressing research priority.
Open Ankle Fractures: What Predicts Infection? A Multicenter Study
Authors: Cooke Margaret E. , Tornetta Paul , Firoozabadi Reza , Vallier Heather , Weinberg Douglas S. , Alton Timothy B. , Dillman Megan R. , Westberg Jerald R. , Schmidt Andrew , Bosse Michael , Leas Daniel P. , Archdeacon Michael , Kakazu Rafael , Nzegwu Ifeanyi , OToole Robert V. , Costales Timothy G. , Coale Max , Mullis Brian , Usmani Rashad H. , Egol Kenneth , Kottmeier Stephen , Sanders David , Jones Cliff , Miller Anna N. , Horwitz Daniel S. , Kempegowda Harish , Morshed Saam , Belaye Tigist , Teague David 
Published: October 2021

Objective:
To identify the patient, injury, and treatment factors associated with an acute infection during the treatment of open ankle fractures in a large multicenter retrospective review. To evaluate the effect of infectious complications on the rates of nonunion, malunion, and loss of reduction.

Design:
Multicenter retrospective review.

Setting:
Sixteen trauma centers.

Patients:
One thousand and 3 consecutive skeletally mature patients (514 men and 489 women) with open ankle fractures.

Main Outcome Measures:
Fracture-related infection (FRI) in open ankle fractures.

Results:
The charts of 1003 consecutive patients were reviewed, and 712 patients (357 women and 355 men) had at least 12 weeks of clinical follow-up. Their average age was 50 years (range 16–96), and average BMI was 31; they sustained OTA/AO types 44A (12%), 44B (58%), and 44C (30%) open ankle fractures. The rate FRI rate was 15%. A multivariable regression analysis identified male sex, diabetes, smoking, immunosuppressant use, time to wound closure, and wound location as independent risk factors for infection. There were 77 cases of malunion, nonunion, loss of reduction, and/or implant failure; FRI was associated with higher rates of these complications (P = 0.01).

Conclusions:
Several patient, injury, and surgical factors were associated with FRI in the treatment of open ankle fractures.

Level of Evidence:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
The Impacts of COVID-19 on Mental Health and Training in US Professional Endurance Athletes
Authors: Roche Megan , Sainani Kristin , Noordsy Douglas , Fredericson Michael 
Published: October 2021

Objective:
We examined how professional athletes are affected by COVID-19. Our primary aim was to assess changes in mental health that occurred after COVID-19 restrictions, and our secondary aim was to assess changes in exercise volume and intensity.

Design:
Cross-sectional study.

Setting:
United States.

Participants:
Strava professional endurance athletes.

Assessment of Risk Factors:
Participants completed a survey, and a subset of participants consented to have their activity data analyzed. The survey included questions on COVID-19 symptoms, exercise, and mental health, as measured by a modified Patient Health Questionnaire.

Main Outcome Measures:
Participants were asked about 2 periods in 2020: before COVID-19 (January 1-March 14) and during COVID-19 (March 15-August 25), and activity data from both periods were downloaded. Activity data consisted of Global Positioning System and self-reported uploads.

Results:
One hundred thirty-one male and female Strava athletes were enrolled, and a subset of athletes (n = 114) consented to have their activity data analyzed. During COVID-19 restrictions, 22.2% of participants reported feeling down or depressed and 27.4% of participants reported feeling nervous or anxious at least half the days in a week compared with 3.8% and 4.6% before COVID-19 restrictions, respectively (P < 0.0001). Activity data revealed a significant increase (P < 0.0001) in exercise minutes per day during COVID-19 (mean = 103.00, SD = 42.1) compared with before COVID-19 restrictions (mean = 92.4, SD = 41.3), with no significant changes in intensity.

Conclusions:
Athletes reported significant increases in feeling down or depressed and nervous or anxious despite an increase in exercise duration during COVID-19. Future research should assess how to support athletes with mental health resources.
Resection or ablation versus transarterial therapy for Child-Pugh A patients with a single small hepatocellular carcinoma
Authors: Suh Young Ju , Jin Young-Joo , Jeong Yujin , Shin Woo Young , Lee Jeong-min , Cho Soongu , Yu Jung Hwan , Lee Jin-Woo 
Published: October 2021

Abstract
Data from a direct comparison of the long-term survival outcomes of surgical resection (SR) or radiofrequency ablation (RFA) versus transarterial therapy in Child-Turcotte-Pugh (CTP)-class A patients with a single small T1/T2 stage hepatocellular carcinoma (HCC) (≤3 cm) are still lacking. This study retrospectively compared the therapeutic outcomes of these treatment types for CTP-A patients with a single small HCC.
Using a nationwide Korean registry, we identified 2314 CTP-A patients with SR (n = 722), RFA (n = 731), or transarterial therapy (n = 861) for a single (≤3 cm) T1/T2 stage HCC from 2008 to 2014. The posttreatment overall survival (OS) of transarterial therapy with either SR or RFA were compared using the Inverse Probability of treatment Weighting (IPW). The median follow-up period was 50 months (range 1–107 months).
After IPW, the cumulative OS rates after SR or RFA were significantly higher than those after transarterial therapy in all subjects (all P values < .05). The OS rates after SR or RFA were better than those after transarterial therapy in patients with the hepatitis B or C virus (all P values < .05), and in patients aged <65 years (all P values < .05). The cumulative OSs between RFA and transarterial therapy were statistically comparable in patients with a 2 to 3 cm HCC and aged ≥65 years, respectively. For all subjects, the weighted Cox proportional hazards model using IPW provided the adjusted hazard ratios (95% confidence interval) for the OS after SR versus transarterial therapy and after RFA versus transarterial therapy of 0.42 (0.30–0.60) (P < .001) and 0.78 (0.61–0.99) (P = .044), respectively.
In CTP-A patients with a single (≤3 cm) T1/T2 HCC, SR or RFA provides a better OS than transarterial therapy, regardless of the HCC etiology (hepatitis B virus or hepatitis C virus), especially in patients with HCC of <2 cm and aged <65 years.
Pembrolizumab-induced focal segmental glomerulosclerosis
Authors: Kim Da Woon , Jeon Hakeong , Kim Sungmi , Lee Wanhee , Kim Hyo Jin , Rhee Harin , Song Sang Heon , Seong Eun Young 
Published: October 2021

Abstract

Rationale:
Focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disorder that leads to end-stage kidney disease. Pembrolizumab, an immune checkpoint inhibitor, is an anti-programmed death 1 (PD-1) immunoglobulin G4 antibody approved for the treatment of advanced melanoma and can cause various renal immune-related adverse events (AEs), including acute kidney injury. Several cases of anti PD-1 therapy-induced glomerulonephritis have been reported so far, but FSGS has seldom been reported.

Patient concerns:
46-year old woman presented to our hospital with generalized edema.

Diagnoses:
Laboratory examination revealed features of nephrotic syndrome, and kidney biopsy confirmed FSGS. After other etiological factors of secondary FSGS were ruled out, she was diagnosed with FSGS caused by pembrolizumab.

Interventions:
She did not resume treatment with pembrolizumab and was treated with irbesartan and furosemide according to the American Society of Clinical Oncology Practice guidelines.

Outcomes:
After 2 months, the features of nephrotic syndrome resolved.

Lessons:
This case provides valuable insight into the etiology of FSGS that can occur as a renal immune-related AE of PD-1 inhibitor therapy. Therefore, patients should undergo evaluation for renal function and urinalysis at baseline and after treatment. If patients treated with PD-1 inhibitors present with renal injury and/or unexplained proteinuria >1 g/day, we would recommend a kidney biopsy to determine the underlying cause and establish an appropriate therapeutic plan.
Simple prognostic markers for optimal treatment of patients with unresectable pancreatic cancer
Authors: Terao Takashi , Kumagi Teru , Hyodo Ichinosuke , Yokota Tomoyuki , Azemoto Nobuaki , Miyata Hideki , Kuroda Taira , Ohno Yoshinori , Tanaka Yoshinori , Shibata Naozumi , Imamura Yoshiki , Kanemitsu Kozue , Miyake Teruki , Koizumi Mitsuhito , Hiasa Yoichi 
Published: October 2021

Abstract
Most patients with pancreatic cancer are ineligible for curative resection at diagnosis, resulting in poor prognosis. This study aimed to evaluate the prognostic factors in patients with unresectable pancreatic cancer.
We retrospectively collected clinical data from 196 patients with unresectable pancreatic cancer who received palliative chemotherapy (N = 153) or palliative care alone (N = 43) from January 2011 to December 2013. Patients’ background data and overall survival were analyzed using the Cox proportional hazard regression model.
In patients receiving palliative chemotherapy (gemcitabine-based regimen, 88.2%) and palliative care alone, the median (range) ages were 68 (43–91) and 78 (53–90) years, and metastatic diseases were present in 80% (N = 123) and 86% (N = 37), respectively. Multivariate analysis in the palliative chemotherapy patients showed that liver metastasis (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.58–3.20, P < .001), neutrophil-to-lymphocyte ratio (>4.5 vs ≤4.5; HR 3.45, 95% CI 2.22–5.36, P < .001), and cancer antigen 19-9 (CA19-9) (≥900 vs <900 U/mL; HR 1.45, 95% CI 1.02–2.05, P = .036) were independent prognostic factors. In those receiving palliative care alone, lung (HR 3.27, 95% Cl 1.46-7.35, p = 0.004) and peritoneum (HR 2.50, 95% CI 1.20–5.18, P = .014) metastases and the C-reactive protein-to-albumin ratio (≥1.3 vs <1.3; HR 3.33, 95% Cl 1.51–7.35, P = .003) were independent prognostic factors. Furthermore, patients with multiple factors had worse prognosis in both groups. Median survival time of palliative chemotherapy patients with risk factors 0, 1, 2, and 3 were 13.1 (95% CI 8.0–16.9), 9.4 (95% CI 7.9–10.1), 6.6 (95% CI 4.9–7.8), and 2.5 (95% CI 1.7–4.0) months, respectively. Similarly, median survival time was 5.7 (95% CI 1.3 -8.0), 2.1 (95% CI 1.5–3.9), and 1.3 (95% CI 0.6–1.7) months, respectively, for palliative care alone patients with risk factor 0, 1, and 2 to 3.
Prognostic markers for pancreatic cancer were neutrophil-to-lymphocyte ratio, liver metastasis, and CA19-9 in patients undergoing palliative chemotherapy and C-reactive protein-to-albumin ratio and lung/peritoneum metastases in patients undergoing palliative care alone. These simple markers should be considered when explaining the prognosis and therapeutic options to patients.
Association between SOCS3 hypermethylation and HBV-related hepatocellular carcinoma and effect of sex and age
Authors: Zheng Hairu , Yan Yanggang , Cheng Jiajia , Yu Shuyong , Wang Yong 
Published: October 2021

Abstract

Background:
Suppressor 3 of cytokine signaling (SOCS3) hypermethylation has been reported to participate in hepatocellular carcinoma (HCC) development and progression, but conflicting results were published. This study aimed to analyze the clinical effects of SOCS3 hypermethylation in HCC and the effects of sex and age on SOCS3 hypermethylation in HCC.

Methods:
Databases were searched for relevant case-control and cohort studies on SOCS3 hypermethylation in HBV-related HCC. In vitro and in vivo studies and studies of patients with serious comorbidities were excluded. Review Manager 5.2 was used to estimate the effects of the results among the selected studies. Forest plots, sensitivity analysis, and bias analysis for the included studies were also conducted.

Results:
Finally, 8 relevant studies met the inclusion criteria. A significant difference in SOCS3 hypermethylation in HCC was found between tumor and nontumor groups (the odds ratio [OR] = 2.01, 95% confidence interval [CI]: 1.48–2.73, P < .00001; P for heterogeneity = .39, I
2 = 5%). The meta-analysis suggested no significant difference in the effect of sex (OR = 1.00, 95% CI: 0.76–1.31, P = .76; P for heterogeneity = .44, I
2 = 0%) and age on SOCS3 hypermethylation in HCC (OR = 1.11, 100% CI: 0.78–1.29, P = .03; P for heterogeneity = .14, I
2 = 36%). Limited publication bias was observed in this study.

Conclusion:
SOCS3 hypermethylation is associated with HBV-related HCC. Sex and age do not affect the association between SOCS3 hypermethylation and HCC. SOCS3 might be a treatment target for HCC.
Cause-specific mortality among patients with different molecular subtypes of T1-2N0M0 breast cancer
Authors: Wang Daoliang , Yi Liang , Zhang Lijun , Wang Zhuo 
Published: October 2021

Abstract
The objective of our study is to investigate mortality pattern and quantitatively assess prognostic risk for cause-specific death among T1-2N0M0 breast cancer survivors.
The representative data of T1-2N0M0 breast cancer patients diagnosed between 2010 and 2016 was retrieved from the Surveillance, Epidemiology, and End Results program. Standardized mortality ratios (SMRs) were calculated taking US population as a reference. Cox regression analysis was conducted to analyze the potential prognostic factors for cause-specific mortality.
A total of 161,966 patients were identified from the Surveillance, Epidemiology, and End Results database. After a median follow-up of 41 months, mortality occurred in 10,567 patients, of which 30.9% and 22.7% were attributed to breast cancer and cardiovascular diseases (CVDs). The standardized mortality ratios of CVD were 4.78, 4.27, 3.78, and 4.95 in patients with HR+/HER2+, HR−/HER2+, HR+/HER2−, and HR−/HER2− breast cancer compared to general US population, respectively. Cox proportional hazards regression analysis showed that the adjusted HRs of breast cancer-specific mortality were 0.999 (95% confidence interval [CI]: 0.879–1.135), 1.454 (95% CI: 1.246–1.697), 2.145 (95% CI: 1.962–2.345) for HR+/HER2+, HR−/HER2+, and HR−/HER2− breast cancer, respectively, as compared with HR+/HER2− subtype; HRs of CVD-specific death were 1.215 (95% CI: 1.041–1.418), 1.391 (95% CI: 1.209–1.601), and 1.515 (95% CI: 1.213–1.892), respectively. In addition, we found that older age at diagnosis, and black race were also independent predictors of CVD-specific death.
In the present study, we revealed the mortality pattern of cause-specific mortality, and identified prognostic factors of overall mortality, breast cancer-specific mortality, and CVD-specific mortality in T1–2N0M0 breast cancer survivors, supporting early detection and more efficient CVD care for these patients.
Enteral administration of alectinib for ALK-positive non-small cell lung cancer in an elderly patient
Authors: Thomas Quentin Dominique , Pautas Marie , Guilhaume Marie-Noëlle , Fiteni Fréderic , Ge Tony , Girard Nicolas 
Published: October 2021

Abstract

Rationale:
Alectinib is a tyrosine kinase inhibitor (TKI) approved for use as first-line metastatic therapy for patients with anaplastic lymphoma kinase-rearranged non-small cell lung cancer. Certain medical conditions related to the tumor lesions may not allow oral administration of TKIs.

Patient concerns:
We hereby report the case of a 90-year-old patient with anaplasic lymphoma kinase-rearranged lung cancer with severely impaired general condition and swallowing disorders.

Diagnosis:
A thoracic computerized tomography (CT)-scan confirmed the presence of a mediastinal tumor lesion explaining the swallowing disorders secondary to recurrent paralysis.

Interventions:
As no oral administration was feasible, alectinib was administered by percutaneous gastrostomy.

Outcomes:
The patient had few side-effects. He presented a major clinical and radiological response. After 2 months of treatment with alectinib, his mini-mental state examination had increased from 8/30 to 23/30. He had a 60% reduction in targeted pulmonary, bone and node lesions according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). After 6 months of treatment, the patient's performance status had evolved from 3 to 1. This improvement in general condition made it possible to remove the feeding tube.

Lessons:
In cases of lung cancer with oncogenic addiction, enteral administration of TKIs should be considered for elderly patients with an impaired general condition.
Efficacy and safety of acupuncture combined with Chinese herbal medicine in the treatment of type 2 diabetes mellitus
Authors: Bao Pengjie , Mi Jia , Yu Ziyang , Liu Le , Zhu Zhiyue , Liu Shilin , Nan Zheng 
Published: October 2021

Abstract

Background:
Diabetes has become a global public health problem and danger to human health. Diabetes is the main cause of blindness, kidney failure, heart attack, stroke, and lower limb amputation. According to the latest epidemiological survey and research, the overall prevalence of diabetes in mainland China is 11.2%, of which type 2 diabetes mellitus (T2DM) accounts for more than 90% acupuncture combined with Chinese herbal medicine have been widely used in the treatment of T2DM. However, we have not found a meta-analysis of their synergistic effects. Therefore, this systematic review and meta-analysis aims to evaluate the efficacy and safety of acupuncture combined with Chinese herbal medicine in the treatment of T2DM.

Method:
From inception up to September 20, 2021, the PubMed, Web of Science, Embase, AMED, Cochrane Library, CNKI, VIP, CBM, and Wanfang databases will be searched. The publication date or language will not be limited. We will apply a combination of medical keywords, including “acupuncture”, “Chinese herbal medicine”, and “type 2 diabetes mellitus”. We will also check other ongoing and unpublished studies in the clinical trial registry. At the same time, we will manually search all reference lists from relevant systematic reviews to find other eligible studies. We will use Review Manager software (REVMAN v5.3 Cochrane Collaboration) to meta-analyze the selected literature. The study for acupuncture combined with Chinese herbal medicine in the treatment of T2DM was a randomized controlled study. Two researchers will independently review the research selection, data extraction, and research quality assessments. Finally, we will observe the outcome measures.

Results:
This study will generate evidence-based data on the treatment of T2DM with acupuncture combined with Chinese herbal medicine and will provide new ideas and treatment modalities to investigate in future research.