bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological Significance of BRCAness in Resectable Pancreatic Ductal Adenocarcinoma and Its Association With Anticancer Drug Sensitivity in Pancreatic Cancer Cells
Authors: Tadehara Masayoshi , Kato Takuya , Adachi Kai , Tamaki Akihiro , Kesen Yurika , Sakurai Yasutaka , Ichinoe Masaaki , Koizumi Wasaburo , Murakumo Yoshiki 
Published: April 2022

Objective
The concept of BRCAness has been proposed as a homologous recombination repair dysfunction triggered by a genetic defect in the BRCA pathway including the BRCA1/2 mutations. A certain number of pancreatic ductal adenocarcinoma (PDAC) patients have BRCAness. However, a large-scale analysis of BRCAness in PDAC has not been performed. In addition, no basic studies have examined the significance of BRCAness in PDAC cell lines.

Methods
Ninety-two patients who underwent surgery for PDAC were enrolled. Formalin-fixed and paraffin-embedded specimens of resected PDACs were used to analyze BRCAness by multiplex ligation-dependent probe amplification. We also analyzed BRCAness in pancreatic cancer cell lines and the sensitivity to cisplatin and olaparib using a colony formation assay.

Results
Of the 92 patients with PDAC, 6 were detected to have BRCAness-positive PDAC (6.5%). No significant differences in overall survival and progression-free survival were observed between the BRCAness-positive and BRCAness-negative groups. One PDAC cell line, KP-2, was positive for BRCAness and was more sensitive to cisplatin and olaparib than the BRCAness-negative cell lines.

Conclusions
Our results revealed that a considerable number of PDACs are positive for BRCAness, suggesting that BRCAness status could be a useful biomarker for selecting anticancer treatments for advanced or relapsed PDAC.
The Role of Estrogen Signaling in Cellular Iron Metabolism in Pancreatic β Cells
Authors: Taneera Jalal , Ali Amjad , Hamad Mawieh 
Published: April 2022

Abstract
Several lines of evidence suggest that estrogen (17-β estradiol; E2) protects against diabetes mellitus and plays important roles in pancreatic β-cell survival and function. Mounting clinical and experimental evidence also suggest that E2 modulates cellular iron metabolism by regulating the expression of several iron regulatory genes, including hepcidin (HAMP), hypoxia-inducible factor 1-α, ferroportin (SLC40A1), and lipocalin (LCN2). However, whether E2 regulates cellular iron metabolism in pancreatic β cells and whether the antidiabetic effects of E2 can be, at least partially, attributed to its role in iron metabolism is not known. In this context, pancreatic β cells express considerable levels of conventional E2 receptors (ERs; mainly ER-α) and nonconventional G protein-coupled estrogen receptors and hence responsive to E2 signals. Moreover, pancreatic islet cells require significant amounts of iron for proper functioning, replication and survival and, hence, well equipped to manage cellular iron metabolism (acquisition, utilization, storage, and release). In this review, we examine the link between E2 and cellular iron metabolism in pancreatic β cells and discuss the bearing of such a link on β-cell survival and function.
Auditing Management of Acute Pancreatitis Using Comprehensive Quality Indicators
Authors: Wee Diana , Izard Stephanie , Raphael Kara , Yang Jeff , Hussein Karim , Wu Grace , Trindade Arvind J. 
Published: April 2022

Objectives
Recently, 40 comprehensive quality indicators in various management domains were created. The aim was to determine if these indicators could be used to audit the management of acute pancreatitis.

Methods
A retrospective study of consecutive patients admitted with acute pancreatitis in 2018 was conducted. Adherence rates with the individual quality indicators were calculated and compared between services.

Results
A total of 320 patients were included in this study. Twenty-eight of the 40 quality indicators (70%) could be used to audit management retrospectively. The medical service was found to have lower adherence rates for quality indicators 12 (initial assessment and risk stratification domain; 11% vs 22%, P = 0.009), 14 (initial management domain; 72% vs 88%, P = 0.003), and 33 (surgery domain; 83% vs 100%, P = 0.006). The surgical service was noted to have statistically significant lower adherence rates for quality indicators 4, 5, and 6 of the etiology domain (54% vs 72%, P = 0.002; 86% vs 96%, P = 0.004; and 45% vs 71%, P < 0.0001, respectively), and 21 of the nutrition domain (76% vs 93%, P < 0.0001).

Conclusions
We show that these quality indicators can be used to audit the management of acute pancreatitis in specific management domains.
Clinicopathological Characteristics of Gastroenteropancreatic Neuroendocrine Tumors
Authors: Şentürk Mustafa , Acar Berkan , Yildirim Mehmet Aykut , Çakir Murat , Küçükkartallar Tevfik , Vatansev Celalettin 
Published: April 2022

Objectives
Gastorenteropancreatic neuroendocrine (GEP-NET) tumors are the second most common tumors of the gastrointestinal tract. We aimed to investigate the clinicopathological features and factors affecting the prognosis of patients with GEP-NET.

Methods
Clinicopathological features of 158 patients were evaluated, including tumor location, TNM stage and grade, pathological features, presence of lymph nodes and distant metastases at the time of diagnosis, maximum tumor diameter and treatment details. Also, follow-up information was analyzed to discover possible prognostic factors.

Results
The most common primary site is pancreas (45.6%, n = 72). Most of the GEP-NETs were nonfunctional (93.6%, n = 148). Of the 158 patients, 94 (59.5%) were grade 1, 46 (29.1%) grade 2, and 18 (11.4%) grade 3. The 1-year, 3-year, and 5-year survival rates were 82.3% (130/158), 61.4% (70/114), and 47.2% (35/74), respectively. In multivariate analysis, histological grade (P = 0.04) and TNM stage (P < 0.001) were independent prognostic factors for survival in patients with GEP-NET.

Conclusions
They are increasing in frequency and are the most common tumors in the pancreas. Nonfunctional tumors made up the majority of cases. The main treatment was surgical resection. Histological grade and TNM stage are independent prognostic factors.
Sarcopenia
Authors: Asama Hiroyuki , Ueno Makoto , Kobayashi Satoshi , Fukushima Taito , Kawano Kuniyuki , Sano Yusuke , Tanaka Satoshi , Nagashima Shuhei , Morimoto Manabu , Ohira Hiromasa , Maeda Shin 
Published: April 2022

Objective
The aim of the study was to clarify the association of skeletal muscle mass and the prognosis of unresectable pancreatic ductal adenocarcinoma (PDAC) treated with gemcitabine plus nab-paclitaxel (GnP).

Methods
We included 124 unresectable PDAC patients who received GnP chemotherapy. Skeletal muscle mass of the third lumbar vertebrae (L3) level was measured by computed tomography immediately before GnP initiation, and the skeletal muscle index (L3-SMI) was calculated. Sarcopenia was defined as L3-SMI less than 42 cm2/m2 in male patients and less than 38 cm2/m2 in female patients.

Results
Sarcopenia was found in 63 patients (50.8%). There was no significant difference in overall survival (OS) between sarcopenia and nonsarcopenia patients; however, in elderly patients (>70 years), the OS of sarcopenia patients was significantly poorer than that of nonsarcopenia patients (390 vs 631 days, respectively; hazard ratio, 2.64; 95% confidence interval, 1.33–5.23). Multivariate analyses in elderly patients revealed that sarcopenia and tumor stage were independent poor prognostic factors. Despite the short OS of elderly sarcopenia patients, there were no significant differences in progression-free survival or response rate.

Conclusions
Sarcopenia diagnosed by L3-SMI is a prognostic factor in elderly patients who receive GnP for unresectable PDAC. However, GnP exhibits a certain efficacy in sarcopenia and nonsarcopenia patients.
Extrapancreatic Complications in Hospitalized Patients With Mild Acute Pancreatitis Are Associated With Poorer Outcomes
Authors: Shah Ishani , Yakah William , Ahmed Awais , Kandasamy Cinthana , Tintara Supisara , Sorrento Cristina , Freedman Steven D. , Kothari Darshan J. , Sheth Sunil G. 
Published: April 2022

Objective
Patients with acute pancreatitis (AP) are at risk for extrapancreatic complications (EPCs) when admitted to the intensive care unit (ICU). We assessed the prevalence of EPCs in non-ICU AP patients and their outcomes.

Methods
We retrospectively studied EPCs in non-ICU AP patients between 2008 and 2018. Outcomes such as length of stay (LOS), inpatient mortality, and 30-day readmission rates were compared between those with and without EPC.

Results
Of the 830 AP patients, 151 (18.1%) had at least 1 EPC. These included urinary tract infection (15.9%), Clostridium difficile infection (17.2%), pneumonia (7.3%), bacteremia (17.2%), acute kidney injury requiring dialysis (3.3%), gastrointestinal bleeding (12.5%), alcohol withdrawal (24.5%), delirium (14.5%), and falls (1.32%). Patients with EPC had increased mean LOS (6.98 vs 4.42 days; P < 0.001) and 30-day readmissions (32.5% vs 19%; P < 0.001). On multivariate regression, EPCs were independently associated with higher LOS (odds ratio, 1.45 [95% confidence interval, 1.36–1.56]; P < 0.001) and 30-day readmissions (odds ratio, 1.94 [95% confidence interval 1.28–2.95]; P < 0.001).

Conclusions
The EPCs are common among noncritical AP patients and contribute to poor outcomes like increased LOS and 30-day readmissions.
Celiac Plexus Neurolysis Is Associated With Decreased Survival in Patients With Pancreatic Cancer
Authors: Zylberberg Haley M. , Nagula Satish , Rustgi Sheila D. , Aronson Anne , Kessel Elizabeth , Kumta Nikhil A. , DiMaio Christopher J. , Lucas Aimee L. 
Published: April 2022

Objective
The aim of this study was to investigate survival in patients who received celiac plexus neurolysis (CPN) compared with patients who received opioids.

Methods
The Surveillance, Epidemiology and End Results–Medicare database was used to identify patients older than 65 years diagnosed with pancreatic cancer between 2007 and 2015. We used claims data to identify patients with a history of CPN and opioid use within 1 year of diagnosis, and other demographic, clinical, and treatment variables. Kaplan-Meier analyses and inverse propensity-weighted adjusted Cox proportional hazard ratios were used to evaluate survival.

Results
We identified 648 patients who underwent CPN (19.0%) compared with 2769 patients who received opioids (81.0%). The median survival and interquartile range for patients who received CPN was 4.0 months (2.0–8.0 months) compared with 7.0 months (3.0–12.0 months) for opioid users (P < 0.0001). After adjusting for confounders and propensity score, the patients who received CPN showed worsened survival (hazard ratio, 1.69; 95% confidence interval, 1.59–1.79).

Conclusions
Pancreatic cancer patients who underwent CPN had decreased survival compared with opioid users. This suggests that opioid sparing methods to reduce pancreatic cancer pain may actually be harmful. Future prospective studies should investigate whether other opioid sparing therapies impact pancreatic cancer survival.
HDAC4 Mediates Smoking-Induced Pancreatic Cancer Metastasis
Authors: Yang Jiyong , Chheda Chintan , Lim Adrian , Hauptschein Dina , Zayou Latifa , Tang Josiah , Pandol Stephen J. , Edderkaoui Mouad 
Published: April 2022

Objective
Cigarette smoking is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). In this project, we investigated the effect of smoking and the role of histone deacetylase 4 (HDAC4) in PDAC invasion and metastasis.

Methods
Cells were treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and cigarette smoke extract and the mRNA levels of HDACs were measured by real-time polymerase chain reaction. Invasion was measured using the Matrigel Invasion Assay. Syngeneic PDAC mice were treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and metastasis measured. Human PDAC primary and metastatic tissues were analyzed by immunohistochemistry.

Results
Levels of HDAC4 mRNA were increased by smoking. Smoking compounds significantly promoted invasion of cancer cells and promoted metastasis of PDAC cells to different organs, including the liver and the lung, whereas inhibition of HDAC4 prevented this effect. The effect of HDAC4 inhibition on preventing smoking-induced metastasis was greater in the liver compared with the lung. We found that HDAC4 is highly expressed in primary and metastatic PDAC tumors.

Conclusions
We found that HDAC4 is the only HDAC induced by smoking among all HDACs analyzed. We found that smoking promotes invasion and metastasis of PDAC cells through a mechanism that involves HDAC4 and that HDAC4 is a promising target for preventing PDAC metastasis.
Validation of the Enriching New-Onset Diabetes for Pancreatic Cancer Model
Authors: Boursi Ben , Patalon Tal , Webb Muriel , Margalit Ofer , Beller Tamar , Yang Yu-Xiao , Chodick Gabriel 
Published: April 2022

Objectives
The Enriching New-onset Diabetes for Pancreatic Cancer (END-PAC) model identified patients at high-risk for pancreatic ductal adenocarcinoma (PDAC) more than 6 months before diagnosis. The current study aimed to validate the END-PAC model using a large, state-mandated health care provider database.

Methods
A retrospective cohort study of patients older than 50 years that had a diagnosis of new-onset diabetes (NOD) between 2006 and 2015. A risk score was assigned according to the END-PAC model. Patients who developed PDAC over the 3-year period after NOD diagnosis were identified using the Israeli National Cancer Registry.

Results
Twenty-three percent (1245/5408) of NOD patients were classified as high-risk, of them 32 (2.6%) developed PDAC. Median follow-up time from NOD detection to PDAC diagnosis was 609 days (interquartile range, 367–997). The hazard ratio for PDAC diagnosis among individuals at the high-risk group compared with the low-risk group was 5.70 (95% confidence interval, 2.93–11.06). Using the high-risk group as the screening threshold, the sensitivity, specificity, positive predictive value and negative predictive value of the model were 54.2%, 76.98%, 2.57%, and 99.4%, respectively. Area under the curve of the model was 0.69.

Conclusions
Our findings support the robustness, generalizability and clinical applicability of the END-PAC model.
Multiarea Brain Activation and Gait Deterioration During a Cognitive and Motor Dual Task in Individuals With Parkinson Disease
Authors: Liu Yan-Ci , Yang Yea-Ru , Yeh Nai-Chen , Ku Pei-Hsin , Lu Chia-Feng , Wang Ray-Yau 
Published: April 2022

Background and Purpose:
In people with Parkinson disease (PD), gait performance deteriorating during dual-task walking has been noted in previous studies. However, the effects of different types of dual tasks on gait performance and brain activation are still unknown. The purpose of this study was to investigate cognitive and motor dual-task walking performance on multiarea brain activity in individuals with PD.

Methods:
Twenty-eight participants with PD were recruited and performed single walking (SW), walking while performing a cognitive task (WCT), and walking while performing a motor task (WMT) at their self-selected speed. Gait performance including walking speed, stride length, stride time, swing cycle, temporal and spatial variability, and dual-task cost (DTC) was recorded. Brain activation of the prefrontal cortex (PFC), premotor cortex (PMC), and supplementary motor areas (SMA) were measured using functional near-infrared spectroscopy during walking.

Results:
Walking performance deteriorated upon performing a secondary task, especially the cognitive task. Also, a higher and more sustained activation in the PMC and SMA during WCT, as compared with the WMT and SW, in the late phase of walking was found. During WMT, however, the SMA and PMC did not show increased activation compared with during SW. Moreover, gait performance was negatively correlated with PMC and SMA activity during different walking tasks.

Discussion and Conclusions:
Individuals with mild to moderate PD demonstrated gait deterioration during dual-task walking, especially during WCT. The SMA and PMC were further activated in individuals with PD when performing cognitive dual-task walking.
Supplemental Digital Content is Available in the Text.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A383).
Clinical and Epidemiological Characterization of Lymphogranuloma Venereum in a Sexually Transmitted Diseases Clinic in Lisbon, 2001 to 2020
Authors: Bonito Frederico , Alves João , Lodhia Zohra , Cordeiro Dora , Borges Vítor , Azevedo Jacinta , Borrego Maria José 
Published: April 2022

Abstract
Between 2001 and 2020, 54 LGV cases were diagnosed in a sexually transmitted disease clinic in Lisbon, most in men who have sex with men (87%), HIV negative (63%), from the anorectal mucosa (72.2%). Cases among heterosexuals were also identified (13%). Surveillance programs irrespective of sexual orientation and HIV status are needed to avoid the morbidity associated with LGV.
Two-Corner Fusion or Four-Corner Fusion of the Wrist for Midcarpal Osteoarthritis? A Multicenter Prospective Comparative Cohort Study
Authors: Duraku Liron S. , Hundepool Caroline A. , Hoogendam Lisa , Selles Ruud W. , van der Heijden Brigitte E. P. A. , Colaris Joost W. , Hovius Steven E. R. ,   Hand-Wrist Study Group, Zuidam J. Michiel 
Published: April 2022

Background:
Midcarpal osteoarthritis is a debilitating wrist pain, and a mainstay treatment is midcarpal fusion. The accepted standard for midcarpal fusion is four-corner fusion, but lately, two-corner fusion (i.e., capitolunate fusion) has gained popularity. This is the first prospective, multicenter, cohort study comparing capitolunate fusion with four-corner fusion for midcarpal osteoarthritis.

Methods:
Patients with scaphoid nonunion advanced collapse or scapholunate advanced collapse wrist of grade 2 to 3 undergoing capitolunate fusion or four-corner fusion between 2013 and 2019 were included. Sixty-three patients (34 with capitolunate fusion, 29 with four-corner fusion) were included. Patient demographics were similar between groups. Patient-Rated Wrist Hand Evaluation questionnaire score, visual analog scale pain score, grip strength, range of motion, and complications were measured at baseline and 3 months and 12 months postoperatively. Complications (i.e., nonunion, hardware migration, conversion to wrist arthrodesis, or arthroplasty) were determined.

Results:
A significant difference in Patient-Rated Wrist Hand Evaluation or visual analog scale pain score at 3 and 12 months postoperatively between the capitolunate fusion and four-corner fusion groups was not found. There were no differences in grip strength between patient groups preoperatively or 12 months postoperatively. At 12 months postoperatively, capitolunate fusion patients had better flexion compared with that in the four-corner fusion group (p = 0.002); there were no differences in complications and reoperation rates between groups.

Conclusions:
Capitolunate fusion and four-corner fusion were comparable in terms of functional scores (i.e., Patient-Rated Wrist Hand Evaluation and visual analog scale pain scores) and complication scores. Capitolunate fusion showed favorable wrist mobility compared with four-corner fusion in treatment of midcarpal osteoarthritis. Capitolunate fusion advantages include use of less material, less need for bone-graft harvesting, and easier reduction of the lunate during fixation.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
An Analytic Method for Calculating Scanner-, Kilovoltage Peak–, and Patient Size–Specific Hounsfield Unit Scale Thresholds for Agatston Score
Authors: Peng Boyu , Jambawalikar Sachin , Einstein Andrew J. 
Published: April 2022

Objective
This study aimed to calculate scanner-, kilovoltage peak (kVp)–, and patient size–specific computed tomography (CT) number thresholds for determining Agatston score (AgSc).

Methods
The proposed method was validated using calcium measurements in an anthropomorphic phantom for 4 CT scanners made by 4 vendors. The derived mass concentration (γ) thresholds were used to calculate kVp- and patient size–specific CT number thresholds. Two models were applied to reduce intrascanner and interscanner AgSc variation, respectively.

Results
The mean error of the modeled CT numbers is 1.8% (0.1%–4.4%). Model 1 has comparable results to the published phantom calibration method for an average-size patient (error, 1.5%; 0.1%–5.1%). The size- and the kVp-dependent fitting of modeled results have R
2 greater than 0.965.

Conclusions
Our results show a potential to enable accurate determination of AgSc under diverse conditions (eg, reduced tube potential) and are more easily applicable to different patient sizes than the phantom calibration method.
Association of Serum Ferritin With Marrow Iron Concentration Using a Three-Dimension Fat Analysis & Calculation Technique Sequence in Postmenopausal Women
Authors: Li Guanwu , Xu Zheng , Wang Yi , Jiang Lei , Chang Shixin , Yuan Wei , Dai Yongming 
Published: April 2022

Abstract

Objective
The aim of the study was to determine whether serum iron and ferritin levels are determinants of iron accumulation in bone marrow using a three-dimension Fat Analysis & Calculation Technique (FACT) sequence.

Methods
We measured spinal marrow R2* using a 3T FACT sequence in 112 postmenopausal women (mean age, 62.6 years; range, 50–82.6 years). Serum iron and ferritin levels were determined in blood specimens. Lumbar spine bone mineral density was measured by dual-energy x-ray absorptiometry. The levels of serum iron and ferritin were evaluated in relation to the spinal marrow R2* values before and after adjustments for potential confounders.

Results
In the unadjusted model, magnetic resonance imaging–based spinal marrow R2* was positively correlated to the levels of serum ferritin (Spearman ρ = 0.436, P < 0.001) and iron (Spearman ρ = 0.245, P = 0.009). Multiple stepwise linear regression analyses (adjusting for age, years since menopause, body mass index, alcohol intake, tobacco use, physical activity, serum lipids profile, biomarkers of bone turnover, and lumbar spine bone density) were performed in 3 separate models with marrow R2* values as potential explanatory variables. The level of serum ferritin, but not iron, was an independent predictor of marrow R2* (standardized β coefficient, 0.302, 95% confidence interval, 0.141–0.509, P = 0.001). Similarly, spinal marrow R2* increased with a linear trend from the lowest (<139 ng/mL) to highest (≥180 ng/mL) serum ferritin quartiles (P for trend = 0.007).

Conclusions
Quantitative assessment of R2* derived from FACT is a fast, simple, noninvasive, and nonionizing method to evaluate marrow iron accumulation.