bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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.
Predictors of poor glycemic control among type 2 diabetes mellitus patients treated with antidiabetic medications
Authors: Wang Jingqing , Li Jie , Wen Chendong , Liu Yan , Ma Hongshan
Published: October 2021

This study aimed to clarify of the predictors of poor glycemic control in type 2 diabetes mellitus (T2DM) patients treated with antidiabetic medications in China.

This study was a retrospective, cross-sectional study based on SuValue database. T2DM patients aged 18 years or older performing glycosylated hemoglobin A1c (HbA1c) examinations from January 1st, 2018 to December 31st, 2018 were included and have been treated with antidiabetic medications for at least 6 months. HbA1c < 7.0% was defined as adequate glycemic control. Multivariate analysis was performed for the factors associated with poor glycemic control.

A total of 13972 T2DM patients were included in this study. The adequate glycemic control rate was 44.04% (n = 6153). In the multivariate analysis, predictors of poor glycemic control include longer T2DM duration (5–10 years vs <5 years and >10 years vs <5 years, odds ratio [OR] = 1.499 and 1.581, P < .001 and P = .008), myocardial infarction (OR = 1.141, P = .041), diabetic neuropathy (OR = 1.409, P < .001), secondary hospital (OR = 1.877, P < .001), underdeveloped regions (OR = 1.786, P < .001), insulin only (OR = 3.912, P < .001), combination of oral antidiabetic agents and/or insulin use (P < .001).

In conclusion, longer T2DM duration, secondary hospital, myocardial infarction, diabetic neuropathy, undeveloped regions and use of polypharmacy and insulin were associated with poor glycemic control among T2DM patients treated with antidiabetic medications. Patient education and training of health care providers may be short-term strategy to achieve adequate glycemic control.
The Role of Inherited Pathogenic CDKN2A Variants in Susceptibility to Pancreatic Cancer
Authors: Kimura Hirokazu , Klein Alison P. , Hruban Ralph H. , Roberts Nicholas J.
Published: October 2021

CDKN2A is cell cycle negative regulator, and the role of CDKN2A in the development of pancreatic ductal adenocarcinoma, which continues to be a lethal cancer, is well-established. Somatic loss of CDKN2A is considered one of the major drivers of pancreatic tumorigenesis. CDKN2A gene is one of the pancreatic cancer susceptibility gene; in addition to melanoma, pathogenic germline CDKN2A variants have been identified in up to 3.3% patients with pancreatic ductal adenocarcinoma depending on family history of disease. Carriers of a known pathogenic germline CDKN2A variant have up to a 12.3-fold increased risk of developing pancreatic cancer. Recently, several studies have demonstrated the benefit of clinical surveillance in patients with pathogenic germline CDKN2A variants. Therefore, identification of patients with a pathogenic germline CDKN2A variant is important for screening of at-risk relatives for pancreatic cancer. It has the potential to lead to the detection of early, potentially curable pancreatic cancer and precursor neoplasms, and reduce mortality. Furthermore, patients with a germline pathogenic CDKN2A variant and somatic loss of CDKN2A may benefit in the future from treatment with targeted therapies, such as a CDK4/6 inhibitor.
Emodin Alleviates Intestinal Barrier Dysfunction by Inhibiting Apoptosis and Regulating the Immune Response in Severe Acute Pancreatitis
Authors: Zhou Qi , Xiang Hong , Liu Han , Qi Bing , Shi Xueying , Guo Wenhui , Zou Jiacheng , Wan Xueting , Wu Wenjing , Wang Zhengpeng , Liu Wenhui , Xia Shilin , Shang Dong
Published: October 2021

Objective

The intestinal barrier injury caused by severe acute pancreatitis (SAP) can induce enterogenous infection, further aggravating the inflammatory reactions and immune responses. This study aimed to test the hypothesis that emodin protects the intestinal function and is involved in the immune response in SAP.

Methods

The network pharmacology was established using the Swiss target prediction and pathway enrichment analysis. The SAP mice model was induced by cerulein (50 μg/kg) and lipopolysaccharide (10 mg/kg) hyperstimulation. The pharmacological effect of emodin in treating SAP was evaluated at mRNA and protein levels by various methods.

Results

The network analysis provided the connectivity between the targets of emodin and the intestinal barrier–associated proteins and predicted the BAX/Bcl-2/caspase 3 signaling pathway. Emodin alleviated the pathological damages to the pancreas and intestine and reduced the high concentrations of serum amylase and cytokines in vivo. Emodin increased the expression of intestinal barrier–related proteins and reversed the changes in the apoptosis-related proteins in the intestine. Simultaneously, emodin regulated the ratio of T helper type 1 (TH1), TH2, TH17, γδ T cells, and interferon γ/interleukin 17 producing γδ T cells.

Conclusions

These findings partly verified the mechanism underlying the regulation of the intestinal barrier and immune response by emodin.
Resection of the Portal-Superior Mesenteric Vein in Pancreatic Cancer
Authors: Groen Jesse V. , van Manen Labrinus , van Roessel Stijn , van Dam Jacob L. , Bonsing Bert A. , Doukas Michael , van Eijck Casper H.J. , Farina Sarasqueta Arantza , Putter Hein , Vahrmeijer Alexander L. , Verheij Joanne , Besselink Marc G. , Groot Koerkamp Bas , Mieog J. Sven D.
Published: October 2021

Objectives

The portal vein (PV)-superior mesenteric vein (SMV) margin is the most affected margin in pancreatic cancer. This study investigates the association between venous resection, tumor invasion in the resected PV-SMV, recurrence patterns, and overall survival (OS).

Methods

This multicenter cohort study included patients who underwent pancreatoduodenectomy for pancreatic cancer (2010–2017). In addition, a systematic literature search was performed.

Results

In total, 531 patients were included, of which 149 (28%) underwent venous resection of whom 53% had tumor invasion in the resected PV-SMV. Patients with venous resection had a significant higher rate of R1 margins (69% vs 37%) and had more often multiple R1 margins (43% vs 16%). Patient with venous resection had a significant shorter time to locoregional recurrence and a shorter OS (15 vs 19 months). At multivariable analyses, venous resection and tumor invasion in the resected PV-SMV were not predictive for time to recurrence and OS. The literature overview showed that pathological assessment of the resected PV-SMV is not adequately standardized.

Conclusions

Only half of patients with venous resection had pathology confirmed tumor invasion in the resected PV-SMV, and both are not independently associated with time to recurrence and OS. The pathological assessment of the resected PV-SMV needs to be standardized.
Rates of Sexually Transmitted Infection Diagnoses Among US Youth With Perinatally and Nonperinatally Acquired HIV
Authors: Neilan Anne M. , DeMonte Justin B. , Foote Julia H. A. , Karalius Brad , Patel Kunjal , Kapogiannis Bill G. , Rudy Bret J. , Huszti Heather , Fernandez M. Isabel , Hudgens Michael G. , Ciaranello Andrea L.
Published: October 2021

Background

Of new sexually transmitted infections (STIs) in the United States, 50% occur among youth aged 15 to 24 years. Previous studies among youth with HIV (YHIV) do not distinguish STI trends among individuals with perinatally (YPHIV) and nonperinatally (YNPHIV) acquired HIV.

Methods

Among 3 Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) studies conducted between 2009 and 2015, we estimated incident diagnoses of trichomonal, bacterial, viral, and overall STIs stratified by sex assigned at birth, mode of HIV acquisition (perinatal [YPHIV] and nonperinatal [YNPHIV]), age (13–17 and 18–24 years), CD4 count (<200, 200–499, and ≥500/μL), and HIV viral load (VL) (<400 and ≥400 copies/mL).

Results

Among 3131 YHIV, across the 3 studies, mean (SD) age was 20.6 (2.6) years, 888 (28%) were female, 2498 (80%) had nonperinatal HIV acquisition recorded, and 2298 (73%) were African American/Black. Mean follow-up was 0.9 (0.3) years. Compared with YPHIV, YNPHIV spent less person-time with VL <400 copies/mL (47% vs. 53%) and more time off antiretroviral therapy (49% vs. 15%), and had higher overall STI rates (males, 65.9 vs. 8.5/100 person-years [PY]; females, 54.7 vs. 17.2/100 PY). Among YPHIV, bacterial STIs were higher during person-time spent with VL ≥400 vs. <400 copies/mL (male YPHIV, 10.9 vs. 0.6/100 PY; female YPHIV, 11.2 vs. 2.9/100 PY); no difference was observed among YNPHIV, which may be due to concurrent acquisition of HIV and other STIs and limited follow-up.

Conclusions

Compared with YPHIV, YNPHIV spent less time on antiretroviral therapy and virologically suppressed; YNPHIV also had higher STI diagnosis rates. Very high STI diagnosis rates among YHIV, including among those without virologic suppression, highlight the importance of youth-focused efforts to support durable virologic suppression and identify and treat STIs.
Telemedicine and visit completion among people with HIV during the coronavirus disease 2019 pandemic compared with prepandemic
Authors: El-Nahal Walid G. , Shen Nicola M. , Keruly Jeanne C. , Jones Joyce L. , Fojo Anthony T. , Lau Bryan , Manabe Yukari C. , Moore Richard D. , Gebo Kelly A. , Lesko Catherine R. , Chander Geetanjali
Published: October 2021

Objectives:

Telemedicine became the primary mode of delivering care during the COVID-19 pandemic. We describe the impact of telemedicine on access to care for people with HIV (PWH) by comparing the proportion of PWH engaged in care prior to and during the COVID-19 pandemic.

Design and methods:

We conducted an observational analysis of patients enrolled in the Johns Hopkins HIV Clinical Cohort, a single-center cohort of patients at an urban HIV subspecialty clinic affiliated with an academic center. Due to the COVID-19 pandemic, the clinic transitioned from in-person to mostly telemedicine visits. We compared patients receiving care in two time periods. The prepandemic period included 2010 people with at least one visit scheduled between 1 September 2019 and 15 March 2020. The pandemic period included 1929 people with at least one visit scheduled between 16 March 2020 and 30 September 2020. We determined the proportion of patients completing at least one of their scheduled visits during each period.

Results:

Visit completion increased significantly from 88% prepandemic to 91% during the pandemic (P = 0.008). Visit completion improved significantly for patients age 20–39 (82 to 92%, P < 0.001), women (86 to 93%, P < 0.001), Black patients (88 to 91%, P = 0.002) and patients with detectable viremia (77 to 85%, P = 0.06) during the pandemic. Only 29% of people who completed at least one telemedicine visit during the pandemic did so as a video (versus telephone) visit.

Conclusion:

During the pandemic when care was widely delivered via telemedicine, visit completion improved among groups with lower prepandemic engagement but most were limited to telephone visits.
Prognostic Utility of Coronary Computed Tomography Angiography-derived Plaque Information on Long-term Outcome in Patients With and Without Diabetes Mellitus
Authors: Tesche Christian , Baquet Moritz , Bauer Maximilian J. , Straube Florian , Hartl Stefan , Leonard Tyler , Jochheim David , Fink David , Brandt Verena , Baumann Stefan , Schoepf U. Joseph , Massberg Steffen , Hoffmann Ellen , Ebersberger Ullrich
Published: October 2021

Purpose:

To investigate the long-term prognostic value of coronary computed tomography angiography (cCTA)-derived plaque information on major adverse cardiac events (MACE) in patients with and without diabetes mellitus.

Materials and Methods:

In all, 64 patients with diabetes (63.3±10.1 y, 66% male) and suspected coronary artery disease who underwent cCTA were matched with 297 patients without diabetes according to age, sex, cardiovascular risk factors, and statin and antithrombotic therapy. MACE were recorded. cCTA-derived risk scores and plaque measures were assessed. The discriminatory power to identify MACE was evaluated using multivariable regression analysis and concordance indices.

Results:

After a median follow-up of 5.4 years, MACE occurred in 31 patients (8.6%). In patients with diabetes, cCTA risk scores and plaque measures were significantly higher compared with nondiabetic patients (all P<0.05). The following plaque measures were predictors of MACE using multivariable Cox regression analysis (hazard ratio [HR]) in patients with diabetes: segment stenosis score (HR=1.20, P<0.001), low-attenuation plaque (HR=3.47, P=0.05), and in nondiabetic patients: segment stenosis score (HR=1.92, P<0.001), Agatston score (HR=1.0009, P=0.04), and low-attenuation plaque (HR=4.15, P=0.04). A multivariable model showed a significantly improved C-index of 0.96 (95% confidence interval: 0.94-0.0.97) for MACE prediction, when compared with single measures alone.

Conclusion:

Diabetes is associated with a significantly higher extent of coronary artery disease and plaque features, which have independent predictive values for MACE. cCTA-derived plaque information portends improved risk stratification of patients with diabetes beyond the assessment of obstructive stenosis on cCTA alone with subsequent impact on individualized treatment decision-making.
Osteogenic Competence and Potency of the Bone Induction Principle: Inductive Substrates That Initiate “Bone: Formation by Autoinduction”
Authors: Ripamonti Ugo , Duarte Raquel , Ferretti Carlo , Reddi A. Hari
Published: October 2021

Thede novoinduction of bone has always been a fascinating phenomenon, keeping skeletal reconstructionists and cellular developmental biologists continuously engaged to finally provide a molecular and cellular approach to the induction of bone formation. A significant advancement was made by the purification and cloning of the human recombinant bone morphogenetic proteins, members of the transforming growth factor-β supergene family. Human bone morphogenetic proteins are powerful inducers of bone in animal models including nonhuman primates. Translation in clinical contexts has however, proven to be surprisingly difficult. This review also describes the significant induction of bone formation by the human transforming growth factor-β3when implanted in heterotopic intramuscular sites of the Chacma baboonPapio ursinus.Large mandibular defects implanted with 250 mg human transforming growth factor-β3in human patients showed significant osteoinduction; however, the induction of bone was comparatively less than the induction of bone inP ursinusonce again highlighting the conundrum of human osteoinduction: is the bone induction principle failing clinical translation?
Factor Influencing Postoperative Enophthalmos After Reconstruction of Orbital Wall Fracture
Authors: Kim Jae-Ik , Chang Minwook
Published: October 2021

Purpose:

To determine factors influencing postoperative enophthalmos after reconstruction of orbital wall fracture.

Method:

Data of consecutive patients who were diagnosed with unilateral medial or inferior orbital wall fracture from March 2013 to February 2020 were retrospectively reviewed. Forty-three patients were included in this study (24 with medial orbital wall fracture and 19 with inferior orbital wall fracture). Their medical records including Hertel exophthalmometry, preoperative computed tomography (CT) scan, and postoperative CT scan were reviewed. The degree of enophthalmos developed was calculated by measuring exophthalmos before surgery and at 6 months after surgery. Patients were classified into 2 groups depending on whether reduction was good after surgery or not. Data (eg, age, gender, onset, fracture size, and so on) were then compared between these 2 groups.

Results:

A total of 43 patients were included in the study. Their mean age was 40.1 years. There were 34 (79.1%) males. The mean onset from trauma to surgery was 8.1 days. Insufficient soft tissue reduction was found in 9 patients through postoperative CT scan. Preoperative mean enophthalmos was – 1.70 mm. Postoperative mean enophthalmos was –0.45 mm after 6 months. The mean fracture size was 213.74 mm2. There was no statistically significant difference in enophthalmos at 6 months after surgery regardless whether the reduction was good or not. Enophthalmos at 6 months after surgery was associated with preoperative fracture size and onset.

Conclusions:

Postoperative enophthalmos development might be associated with preoperative fracture size and onset. Delayed operation in case of large orbital wall fracture might lead to undesired result. Thus, surgeons should keep that in mind.
Leukocyte and its Subtypes as Predictors of Short-Term Outcome in Cardiogenic Shock Complicating Acute Myocardial Infarction: A Cohort Study
Authors: Sasmita Bryan Richard , Zhu Yuansong , Gan Hongbo , Hu Xiankang , Xue Yuzhou , Xiang Zhenxian , Liu Gang , Luo Suxin , Huang Bi
Published: October 2021

Background:

Patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) are at high risk of death. Inflammation is involved in both CS and AMI, and our present study aimed to investigate the changes of leukocyte and its subtypes as well as their prognostic value in patients with CS complicating AMI.

Methods:

Data of 217 consecutive patients with CS complicating AMI were analyzed. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite events of major adverse cardiovascular events (MACE) including 30-day all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal hemorrhage and nonfatal stroke. The association of leukocyte and its subtypes with the endpoints was analyzed by Cox regression analysis.

Results:

Leukocyte and its subtypes including neutrophil, eosinophil, lymphocyte, monocyte and basophil were all statistically significant between survivors and nonsurvivors (all P < 0.05). Among the leukocyte subtypes, eosinophil had the highest predictive value for 30-day all-cause mortality (AUC = 0.799) and the composite of leukocyte and its subtypes improved the predictive power (AUC = 0.834). The 30-day mortality and MACE K-M curves of leukocyte and its subtypes reveal a distinct trend based on the cut-off value determined by Youden Index (all log rank P < 0.001). After multivariable adjustment, high leukocyte (>11.6 × 109/L) (HR 1.815; 95%CI 1.134, 2.903; P = 0.013), low eosinophil (<0.3%) (HR 2.562; 95%CI 1.412, 4.648; P = 0.002) and low basophil (≤0.1%) (HR 1.694; 95%CI 1.106, 2.592; P = 0.015) were independently associated with increased risk of 30-day mortality. Similarly, high leukocyte (>11.6 × 109/L) (HR 1.894; 95%CI 1.285, 2.791; P = 0.001), low eosinophil (<0.3%) (HR 1.729; 95%CI 1.119, 2.670; P = 0.014) and low basophil (≤0.1%) (HR 1.560; 95%CI 1.101, 2.210; P = 0.012) were independently associated with increased risk of 30-day MACE.

Conclusions:

Leukocyte and its subtypes changed significantly in patients with CS complicating AMI. In addition to leukocyte, eosinophil and basophil also served as independent prognostic factors for 30-day outcomes. Moreover, as the composite of leukocyte and its subtypes increased the predictive power, thus leukocyte and its subtypes, especially eosinophil and basophil should be taken into consideration for the current risk stratification model.
State firearm laws and nonfatal firearm injury-related inpatient hospitalizations: A nationwide panel study
Authors: Neufeld Miriam Y. , Poulson Michael , Sanchez Sabrina E. , Siegel Michael B.
Published: October 2021

BACKGROUND

Firearm injury remains a major cause of morbidity and mortality in the United States. Because of prior lack of comprehensive data sources, there is a paucity of literature on nonfatal firearm injury. Associations have previously been shown between state-level firearm laws and firearm fatalities, but few studies have examined the effects of these laws on nonfatal firearm hospitalization rates. Our objective was to examine the relationship between state firearm laws and firearm injury-related hospitalization rates across all 50 states over a 17-year period.

METHODS

In this panel study design, we used fixed effects multivariate regression models to analyze the relationship between 12 laws and firearm state-level injury-related hospitalization rates from 2000 to 2016 using the RAND Corporation Inpatient Hospitalizations for Firearm Injury Database. We used difference-in-differences to determine the impact of law passage in a given state compared with those states without the law, controlling for state-level covariates. The main outcome measure was the change in annual firearm injury-related inpatient hospitalization rates after passage or repeal of a state-level firearm law.

RESULTS

Examining each law individually, passage of violent misdemeanor, permitting, firearm removal from domestic violence offenders, and 10-round limit laws were associated with significant firearm injury-related hospitalization rate reductions. Examining multiple laws in the same model, passage of violent misdemeanor laws was associated with a 19.9% (confidence interval, 11.6%–27.4%) reduction, and removal of firearms from domestic violence offenders was associated with a 17.0% (confidence interval, 9.9%–23.6%) reduction in hospitalization rates.

CONCLUSION

State laws related to preventing violent offenders from possessing firearms are associated with firearm injury-related hospitalization rate reductions. Given significant physical, mental, and social burdens of nonfatal firearm injury, determining the efficacy of firearm-related policy is critical to violence and injury prevention efforts.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level IV.
Focused Neuromuscular Ultrasound Approach for the Diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy
Authors: Yun Chelsea J. , Crump Nicholas , Puckett Meaghan , Cartwright Michael S.
Published: October 2021

Purpose:

Previous ultrasonographic studies of individuals with chronic inflammatory demyelinating polyneuropathy (CIDP) have shown nerve enlargement at several sites. This prospective study compares only the bilateral median and ulnar nerves of individuals with CIDP with reference values to determine the clinical usefulness of this focused approach as a diagnostic tool.

Methods:

The cross-sectional area, echogenicity, and vascularity of the bilateral median and ulnar nerves of 25 subjects with CIDP were measured using ultrasound. Nineteen had typical CIDP based on the European Federation of Neurological Societies and the Peripheral Nerve Society guidelines, whereas six had atypical CIDP and were diagnosed based on clinical impression.

Results:

Focal nerve enlargement was found in at least one segment in all subjects. Subjects with typical CIDP had larger cross-sectional areas compared with subjects with atypical CIDP.

Conclusion:

A focused ultrasound study, involving only the median and ulnar nerves, is sensitive for the detection of nerve enlargement in CIDP. Measuring the cross-sectional area of the median and ulnar nerves is clinically feasible and may help establish the diagnosis of CIDP.
Phylogenetic and antimicrobial drug resistance analysis of Vibrio cholerae O1 isolates from Ghana
Authors: Opintan Japheth A. , Will Robert C. , Kuma George K. , Osei Mary , Akumwena Amos , Boateng Gifty , Owusu-Okyere Godfred , Antwi Lorreta , Opare David , Pragasam Agila Kumari , Vasudevan Karthick , Srivastava Sunil Kumar , Balaji Veeraraghavan , Newman Mercy J. , Dougan Gordon , Mutreja Ankur
Published: October 2021

We investigated the evolution, phylogeny and antimicrobial resistance of

Vibrio cholerae

O1 isolates (VCO1) from Ghana. Outbreak and environmental sources of VCO1 were characterized, whole-genome sequenced and compared to globally available seventh pandemic (7P) strains of

V. cholerae

at SNP resolution. Final analyses included 636 isolates. Novel Ghanaian isolates clustered into three distinct clades (clades 1, 2 and 3) in wave 3 of the 7P lineage. The closest relatives of our novel Ghanaian isolates were from Benin, Cameroon, Togo, Niger and Nigeria. All novel Ghanaian isolates were multi-drug resistant. Environmental isolates clustered into clade 2, despite being isolated years later, showing the possibility of persistence and re-emergence of older clades. A lag phase of several years from estimated introduction to reported cases suggests pathogen persistence in the absence of reported cholera cases. These results highlight the importance of deeper surveillance for understanding transmission routes between bordering countries and planning tailored vaccination campaigns in an effort to eradicate cholera.
Multi-model Order ICA: A Data-driven Method for Evaluating Brain Functional Network Connectivity Within and Between Multiple Spatial Scales
Authors: Meng Xing , Iraji Armin , Fu Zening , Kochunov Peter , Belger Aysenil , Ford Judy M. , McEwen Sara , Mathalon Daniel H. , Mueller Bryon A. , Pearlson Godfrey , Potkin Steven G. , Preda Adrian , Turner Jessica , van Erp Theo G.M. , Sui Jing , Calhoun Vince D.
Published: October 2021

Background

While functional connectivity is widely studied, there has been little work studying functional connectivity at different spatial scales. Likewise, the relationship of functional connectivity between spatial scales is unknown.

Methods

We proposed an independent component analysis (ICA) - based approach to capture information at multiple model orders (component numbers) and to evaluate functional network connectivity (FNC) both within and between model orders. We evaluated the approach by studying group differences in the context of a study of resting fMRI (rsfMRI) data collected from schizophrenia (SZ) individuals and healthy controls (HC). The predictive ability of FNC at multiple spatial scales was assessed using support vector machine (SVM)-based classification.

Results

In addition to consistent predictive patterns at both multiple-model orders and single model orders, unique predictive information was seen at multiple-model orders and in the interaction between model orders. We observed that the FNC between model order 25 and 50 maintained the highest predictive information between HC and SZ. Results highlighted the predictive ability of the somatomotor and visual domains both within and between model orders compared to other functional domains. Also, subcortical-somatomotor, temporal-somatomotor, and temporal-subcortical FNCs had relatively high weights in predicting SZ.

Conclusions

In sum, multi-model order ICA provides a more comprehensive way to study FNC, produces meaningful and interesting results which are applicable to future studies. We shared the spatial templates from this work at different model orders to provide a reference for the community, which can be leveraged in regression-based or fully automated (spatially constrained) ICA approaches.

Impact Statement

Multi-model order ICA provides a comprehensive way to study brain functional network connectivity within and between multiple spatial scales, highlighting findings that would have been ignored in single model order analysis. This work expands upon and adds to the relatively new literature on resting fMRI-based classification and prediction. Results highlighted the differentiating power of specific intrinsic connectivity networks on classifying brain disorders of schizophrenia patients and healthy participants, at different spatial scales. The spatial templates from this work provide a reference for the community, which can be leveraged in regression-based or fully automated ICA approaches.
Early visual processing as a marker of disease, not vulnerability: Event-related potential (ERP) evidence from 22q11.2 deletion syndrome, a population at high risk for schizophrenia
Authors: Francisco Ana A. , Foxe John J. , Horsthuis Douwe J. , Molholm Sophie
Published: October 2021

We investigated visual processing in 22q11.2 deletion syndrome (22q11.2DS), a condition characterized by an increased risk for schizophrenia. Visual processing differences have been described in schizophrenia but remain understudied early in the disease course. Electrophysiology was recorded during a visual adaptation task with different interstimulus intervals to investigate visual processing and adaptation in 22q11.2DS (with (22q+) and without (22q-) psychotic symptoms), compared to control and idiopathic schizophrenia groups. Analyses focused on early windows of visual processing. While increased amplitudes were observed in 22q11.2DS in an earlier time window (90-140 ms), decreased responses were seen later (165-205 ms) in schizophrenia and 22q+. 22q11.2DS, and particularly 22q-, presented increased adaptation effects. We argue that while amplitude and adaptation in the earlier time window may reflect specific neurogenetic aspects associated with a deletion in chromosome 22, amplitude in the later window may be a marker of the presence of psychosis and/or of its chronicity/severity.
Sample Size Analysis for Machine Learning Clinical Validation Studies
Authors: Goldenholz Daniel M. , Sun Haoqi , Ganglberger Wolfgang , Westover M. Brandon
Published: October 2021

OBJECTIVE

Before integrating new machine learning (ML) into clinical practice, algorithms must undergo validation. Validation studies require sample size estimates. Unlike hypothesis testing studies seeking a p-value, the goal of validating predictive models is obtaining estimates of model performance. Our aim was to provide a standardized, data distribution- and model-agnostic approach to sample size calculations for validation studies of predictive ML models.

MATERIALS AND METHODS

Sample Size Analysis for Machine Learning (SSAML) was tested in three previously published models: brain age to predict mortality (Cox Proportional Hazard), COVID hospitalization risk prediction (ordinal regression), and seizure risk forecasting (deep learning). The SSAML steps are: 1) Specify performance metrics for model discrimination and calibration. For discrimination, we use area under the receiver operating curve (AUC) for classification and Harrell’s C-statistic for survival models. For calibration, we employ calibration slope and calibration-in-the-large. 2) Specify the required precision and accuracy (≤0.5 normalized confidence interval width and ±5% accuracy). 3) Specify the required coverage probability (95%). 4) For increasing sample sizes, calculate the expected precision and bias that is achievable. 5) Choose the minimum sample size that meets all requirements.

RESULTS

Minimum sample sizes were obtained in each dataset using standardized criteria.

DISCUSSION

SSAML provides a formal expectation of precision and accuracy at a desired confidence level.

CONCLUSION

SSAML is open-source and agnostics to data type and ML model. It can be used for clinical validation studies of ML models.
Continuous land cover change detection in a critically endangered shrubland ecosystem using neural networks
Authors: Moncrieff Glenn R.
Published: October 2021

Existing efforts to continuously land cover change using satellite image time-series have mostly focused on forested ecosystems in the tropics and northern hemisphere. The notable difference in reflectance that occurs following deforestation allows land cover change to be detected with relative accuracy. Less progress has been made in detecting change in low productivity, disturbanceprone vegetation such as grasslands and shrublands, where natural dynamics can be difficult to distinguish from habitat loss. Renosterveld is a hyperdiverse, critically endangered shrubland ecosystem in South Africa with less than 5-10% of its original extent remaining in small, highly fragmented patches. I demonstrate that direct classification of satellite image time series using neural networks can accurately detect the transformation of Renosterveld within a few days of its occurrence, and that trained models are suitable for operational continuous monitoring. A dataset of precisely dated vegetation change events between 2016 and 2021 was obtained from daily, high resolution Planet labs satellite data. This dataset was then used to train and evaluate 1D convolutional neural networks and Transformers to continuously detect land cover change events in multivariate time-series of vegetation activity of Sentinel 2 satellite data as it becomes available. The best model correctly identified 89% of land cover change events at the pixel-level, achieving a f-score of 0.93, a 79% improvement over the f-score of 0.52 achieved using a method designed for forested ecosystems based on trend analysis. Models have been deployed to operational use and are producing updated detections of habitat loss every 10 days. There is great potential for supervised approaches to continuous monitoring of habitat loss in ecosystems with complex natural dynamics. A key limiting step is the development of accurately dated datasets of land cover change events with which to train machine learning classifiers.
Fruit colour and range size interact to influence diversification
Authors: Hill Adrian P. , Torres Jiménez Maria Fernanda , Chazot Nicolas , Cássia-Silva Cibele , Faurby Søren , Bacon Christine D.
Published: October 2021

Aim

Different fruit colours are associated with dispersal by different frugivores, largely based on colour vision type. Frugivore mobility affects overall range size for the plant being dispersed. Here we determine the interaction between different fruit colours, range sizes, and diversification rates by testing two hypotheses: That (1) fruit colours attractive to birds have larger range sizes due to their higher dispersal ability, and that (2) different frugivore disperser groups, bird or mammal, leads to different diversification rate at different range size, where intermediate range size leads to the highest diversification rate.

Location

Global.

Time period

Contemporary (or present)

Major taxa studied

Palms (Arecaceae)

Methods

Using model selection, we identified three groups of colours with similar diversification rate and likely disperser. Range sizes were estimated and categorized species as small, intermediate, or large-ranged. For model selection and to determine the relationship beween fruit color, range size and diversification rate we used Multi-State Speciation and Extinction (MuSSE) models.

Results

Species with intermediate range size had the highest net diversification for all three fruit colour groups. Bird-dispersed palms more likely diversified at small than at large range size while mammal-dispersed palms more likely diversified at larger range size than small. Fruit colours associated with mammal dispersal had more large-ranged species than colours associated with bird dispersal.

Main conclusions

The associated between intermediate range size and higher diversification rate indicates that spatial factors that affect diversification at small and large range sizes result in higher diversification at intermediate ranges. We find striking differences in diversification rate within each range size category between fruit color groups. This suggests that the relationship between diversification rate and range size depends on the specific frugivorous dispersers and their dispersal patterns. This study reveals how fruit traits alter dispersal patterns and how that, in turn, influences diversification.
Effect of channel assembly (KCNQ1 or KCNQ1 + KCNE1) on the response of zebrafish IKs to IKs inhibitors and activators
Authors: Haverinen Jaakko , Hassinen Minna , Vornanen Matti
Published: October 2021

In cardiac myocytes, the slow component of the delayed rectifier K+ current (IKs) ensures repolarization of action potential during beta-adrenergic activation or when other repolarizing K+ currents fail. As a key factor of cardiac repolarization IKs should be present in model species used for cardiovascular drug screening, preferably with pharmacological characteristics similar to those of the human IKs. To this end, we investigated the effects of inhibitors and activators of the IKs on KCNQ1 and KCNQ1+KCNE1 channels of the zebrafish, an important model species, in Chinese hamster ovary cells. Inhibitors of IKs, chromanol 293B and HMR-1556, inhibited zebrafish IKs channels with approximately similar potency as that of mammalian IKs. Chromanol 293B concentration for half-maximal inhibition (IC50) of zebrafish IKs was at 13.1±5.8 and 13.4±2.8 μM for KCNQ1 and KCNQ1+KCNE1 channels, respectively. HMR-1556 was a more potent inhibitor of zebrafish IKs with IC50=0.1±0.1 μM and 1.5±0.8 μM for KCNQ1 and KCNQ1+KCNE1 channels, respectively. R-L3 and mefenamic acid, generally identified as IKs activators, both inhibited zebrafish IKs. R-L3 almost completely inhibited zebrafish IKs generated by KCNQ1 and KCNQ1+KCNE1 channels with similar affinity (IC50 1.1±0.4 and 1.0±0.4 μM, respectively). Mefenamic acid partially blocked zebrafish KCNQ1 (IC50=9.5±4.8 μM) and completely blocked KCNQ1+KCNE1 channels (IC50=3.3±1.8 μM). Although zebrafish IKs responds to IKs inhibitors in the same way as mammalian IKs, its response to activators is atypical, probably due to the differences in the binding domain of KCNE1 to KCNQ1. Therefore, care must be taken when translating the results from zebrafish to humans.
Antithetical contribution of primary and non-primary auditory cortex while listening to speech in noisy scenes
Authors: Hausfeld Lars , Hamers Iris M. H. , Formisano Elia
Published: October 2021

Invasive and non-invasive electrophysiological measurements during “cocktail-party”-like listening indicate that neural activity in the human auditory cortex (AC) “tracks” the envelope of relevant speech. Due to the measurements’ limited coverage and/or spatial resolution, however, the distinct contribution of primary and non-primary auditory areas remains unclear. Using 7-Tesla fMRI, here we measured brain responses of participants attending to one speaker, without and with another concurrent speaker. Using voxel-wise modeling, we observed significant speech envelope tracking in bilateral Heschl’s gyrus (HG) and right middle superior temporal sulcus (mSTS), despite the sluggish fMRI responses and slow temporal sampling. Neural activity was either positively (HG) or negatively (mSTS) correlated to the speech envelope. Further analyses comparing the similarity between spatial response patterns in theconcurrent speakersandsingle speakerconditions indicated that whereas tracking in HG reflected both relevant and (to a lesser extent) non-relevant speech, right mSTS selectively represented the relevant speech signal. Additionally, in right mSTS, the similarity strength correlated with the participant’s comprehension of relevant speech. These results indicate that primary and non-primary AC antithetically process ongoing speech suggesting a push-pull of acoustic and linguistic information.
DLA-Ranker: Evaluating protein docking conformations with many locally oriented cubes
Authors: Behbahani Yasser Mohseni , Laine Élodie , Carbone Alessandra
Published: October 2021

Proteins ensure their biological functions by interacting with each other, and with other molecules. Determining the relative position and orientation of protein partners in a complex remains challenging. Here, we address the problem of ranking candidate complex conformations toward identifying near-native conformations. We propose a deep learning approach relying on a local representation of the protein interface with an explicit account of its geometry. We show that the method is able to recognise certain pattern distributions in specific locations of the interface. We compare and combine it with a physics-based scoring function and a statistical pair potential.
Hematopoietic stem and progenitor cells improve survival from sepsis by boosting immunomodulatory cells
Authors: Morales-Mantilla Daniel E. , Kain Bailee , Le Duy , Flores Anthony R. , Paust Silke , King Katherine Y.
Published: October 2021

New therapeutic strategies to reduce sepsis-related mortality are urgently needed, as sepsis accounts for 1 in 5 deaths worldwide. Since hematopoietic stem and progenitor cells (HSPCs) are responsible for producing blood and immune cells, including in response to immunological stress, we explored their potential for treating sepsis. In a mouse model of Group A Streptococcus (GAS)-induced sepsis, severe immunological stress was associated with significant depletion of bone marrow HSPCs and mortality within approximately 5-7 days. We hypothesized that the inflammatory environment of GAS infection drives rapid HSPC differentiation and depletion that can be rescued by infusion of donor HSPCs. Indeed, infusion of 10,000 naïve HSPCs into GAS-infected mice resulted in rapid myelopoiesis and a 50-60% increase in overall survival. Surprisingly, mice receiving donor HSPCs displayed a similar pathogen load compared to untreated mice. Flow cytometric analysis revealed a significantly increased number of myeloid-derived suppressor cells in HSPC-infused mice, which correlated with reduced inflammatory cytokine levels and restored HSPC levels. These findings suggest that HSPCs play an essential immunomodulatory role that may translate into new therapeutic strategies for sepsis.