bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of CancelRx on discontinuation of controlled substance prescriptions: an interrupted time series analysis
Authors: Watterson Taylor L. , Stone Jamie A. , Gilson Aaron , Brown Roger , Xiong Ka Z. , Schiefelbein Anthony , Ramly Edmond , Kleinschmidt Peter , Semanik Michael , Craddock Lauren , Pitts Samantha I. , Woodroof Taylor , Chui Michelle A. 
Published: February 2022

Abstract
Background
Prescription opioid misuse is a serious national crisis; in 2018 the top drugs involved in prescription overdose deaths included pain medications (opioids), benzodiazepines, and stimulants. Health information technology (health IT) provides a means to address this crisis through technologies that streamline the prescribing and discontinuation process. CancelRx is a health IT function that communicates when medications, such as controlled substances, are discontinued at the clinic and therefore should not be filled at the pharmacy. Prior to CancelRx, the communication of discontinued medications was a manual process, requiring the patient or a clinic staff member to personally contact the pharmacy to inform them of the change. The objective of this study was to assess how controlled substance medication discontinuations were communicated over time, before and after the implementation of CancelRx.

Methods
Secondary data from a midwestern academic health system electronic health record and pharmacy platform were collected 12-months prior to CancelRx implementation and for 12-months post implementation. The study utilized an interrupted time series analysis (ITSA) to capture the percentage of controlled substance medications that were discontinued in the clinic’s electronic health record and discontinued in the pharmacy’s dispensing software. The ITSA plotted the percentage of successful discontinuation messages over time, particularly after the health system’s implementation of CancelRx, a novel technology.

Results
After CancelRx implementation there was an immediate (change = 77.7 percentage point) and significant (p < 0.001) increase in the number of controlled substance medications that were successfully discontinued at the pharmacy after being discontinued in the clinic. This change was sustained in the year following CancelRx (slope = 0.03 pp, 95% CI − 0.050 to 0.110) and did not revert to pre-CancelRx levels. The health IT functionality was able to effectively complete discontinuation tasks and potentially reduce workload for clinic staff.

Conclusions
Overall, this study demonstrates the role that technology can play in promoting communication between clinics and pharmacies, especially when medications such as controlled substances are discontinued.
Keeping calm on a busy day—an interpersonal skill home care patients desire in health workers: hermeneutical phenomenological method
Authors: Watz Siw , Ingstad Kari 
Published: February 2022

Abstract
Background
In Western countries, many health and social care provisions have been transferred to primary care, and most older patients wish to remain in their own homes for as long as possible. For older patients who live alone, health workers could be their only personal contacts. Hence, health workers’ personal skills affect their relationships with these patients. Accordingly, this study aimed to shed light on the interpersonal skills needed by health workers to establish good relationships with older home care patients and highlight the importance of interpersonal skills training in nursing education.

Methods
This study adopted a hermeneutical phenomenological approach. The qualitative method was used to elicit data on patients’ perspectives. Ten home care patients were interviewed individually in their own homes between December 2019 and January 2020.

Results
Despite individual variations, health workers’ interpersonal skills are of significance with regard to the social well-being of patients living at home. The findings revealed that patients want health workers to be mentally present, congruent in their communications, calm and relaxed during the available time spent with them, and capable of facilitating autonomy.

Conclusions
It is important to present patients’ perspectives to ensure that nursing education is geared towards patients’ best interests.

Trial registration number
The Norwegian Centre for Research Data (NSD): 953937.
Pan-cancer analysis of oncogenic role of Programmed Cell Death 2 Like (PDCD2L) and validation in colorectal cancer
Authors: Gao Huabin , Xu Cheng , Liang Jiangtao , Ge Songhan , Zhang Fenfen , Tuo Ying , Shi Huijuan , Han Anjia 
Published: February 2022

Abstract
Background
Programmed Cell Death 2 Like (PDCD2L) correlates with cell proliferation, apoptosis and mouse embryonic development. However, the role of PDCD2L in human cancers is unclear.

Methods
Multiple bioinformatic methods, in vitro function experiments and validation were performed to clarify the oncogenic role of PDCD2L in human cancers.

Results
Our study found that PDCD2L was aberrantly expressed in multiple types of human cancers, and associated with clinical stage and molecular subtype. Furthermore, overexpression of PDCD2L predicted poor overall survival in adrenocortical carcinoma(ACC), kidney chromophobe(KICH), acute myeloid leukemia(LAML), brain lower grade glioma(LGG),liver hepatocellular carcinoma(LIHC), mesothelioma(MESO), uveal melanoma(UVM) and poor diseases free survival in ACC, bladder urothelial carcinoma(BLCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), kidney renal clear cell carcinoma(KIRC), kidney renal papillary cell carcinoma(KIRP), LGG, LIHC, and UVM. PDCD2L expression was negatively associated with cancer associated fibroblast in breast invasive carcinoma (BRCA), lung squamous cell carcinoma (LUSC), sarcoma (SARC), stomach adenocarcinoma (STAD) and testicular germ cell tumors (TGCT). Mechanically, we found that PDCD2L expression was associated with apoptosis, invasion and cell cycle by investigating single cell sequencing data. For further validation, PDCD2Lwas highly expressed in colorectal cancer (CRC) cell lines and tissue samples compared with the normal colon cell line and non-tumor adjacent colorectal mucosa tissues. PDCD2L knockdown induced the apoptosis and proliferation of CRC cells.

Conclusions
Our study shows that the oncogenic role of PDCD2L in various cancers and PDCD2L could be served as a biomarker of CRC.
Skeletal muscle wasting and long-term prognosis in patients undergoing rectal cancer surgery without neoadjuvant therapy
Authors: Giani Alessandro , Famularo Simone , Fogliati Alessandro , Riva Luca , Tamini Nicolò , Ippolito Davide , Nespoli Luca , Braga Marco , Gianotti Luca 
Published: February 2022

Abstract
Background
Derangement of body composition has been associated with dismal long-term survival in several gastrointestinal cancers including rectal tumors treated with neoadjuvant therapies. The role of specific preoperative anthropometric indexes on the oncologic outcomes of patients undergoing upfront surgery for rectal cancer has not been investigated.
The aim of the study is to evaluate the association of body composition and overall survival in this specific cohort.

Methods
Lumbar computed tomography images, obtained within the 30 days previous to surgery, between January 2009 and December 2016, were used to calculate population-specific thresholds of muscle mass (sarcopenia), subcutaneous and visceral adiposity, visceral obesity, sarcopenic obesity, and myosteatosis. These body composition variables were related with overall survival (OS), tumor-specific survival (TSS), and disease-free survival (DFS). OS, TSS, and DFS were evaluated by the Kaplan-Meier method. Cox regression analysis was used to identify independent predictors of mortality, tumor-specific mortality, and recurrence, and data were presented as hazard ratio (HR) and 95% confidence interval (CI).

Results
During the study period, 411 patients underwent rectal resection for cancer, and among these, 129 were without neoadjuvant chemoradiation. The median follow-up was 96.7 months. At the end of the follow-up, 41 patients (31.8%) had died; of these, 26 (20.1%) died for tumor-related reasons, and 36 (27.1%) experienced disease recurrence.
One-, three-, and five-year OS was 95.7%, 86.0%, and 76.8% for non-sarcopenic patients versus 82.4%, 58.8%, and 40.0% for sarcopenic ones respectively (p < 0.001). Kaplan-Meier survival curves comparing sarcopenic and non-sarcopenic patients showed a significant difference in terms of OS (log-rank < 0.0001). Through multivariate Cox regression, overall mortality risk was associated only with sarcopenia (HR 1.96; 95%CI 1.03–3.74; p = 0.041). Disease stage IV and III (HR 13.75; 95% CI 2.89–65.6; p < 0.001 and HR 4.72; 95% CI 1.06–21.1; p = 0.043, respectively) and sarcopenia (HR 2.62; 95% CI 1.22–5.6; p = 0.013) were independently associated with TSS. The other body composition indexes investigated showed no significant association with prognosis.

Conclusions
These results support the inclusion of body composition assessment for prognostic stratification of rectal cancer patients undergoing upfront resection.
Toxicity study in a pig model of intraperitoneal collagenase as an “enzymatic scalpel” directed to break stroma in order to generate a new perspective for peritoneal carcinomatosis approach: an experimental research
Authors: Garcia-Arranz M. , Villarejo-Campos P. , Barambio J. , Garcia Gomez-Heras S. , Vega-Clemente L. , Guadalajara H. , García-Olmo D. 
Published: February 2022

Abstract
Background
This study aimed to measure the toxicity resulting from collagenase administration to the peritoneal cavity in a pig model as a preliminary step to break down the stroma surrounding tumors.

Methods
Eight pigs were treated with 2 different collagenase concentrations previously tested in rats by our group. Time and temperature were controlled using a peritoneal lavage system (PRS System, Combat Medical Ltd.) identical to that used in human surgeries through hyperthermic intraperitoneal chemotherapy (HIPEC); 2 additional pigs were treated with peritoneal lavage only. Samples of blood and peritoneal fluid were collected pre-treatment, immediately after treatment, and 24 h postoperatively. In addition, histological studies and blood collagenase levels were measured.

Results
No complications were observed during the surgeries. Intraoperative images evidenced the release of peritoneal tissue during collagenase treatment. After surgery, the animals showed no signs of pain. Diet and mobility were normal at 4 h postoperatively, and there were no significant differences in hematologic or biochemical parameters. Quantification of MMP1 and MMP2 in all samples as measured by absorbance showed no differences in blood collagenase levels between pre-treatment, post-treatment, and 24 h postoperatively.
None of the animals treated with collagenase showed peritoneal adhesions during the second surgery. Histologically, peritoneal organs and serous structures did not show any microscopic alterations associated with collagenase treatment in any group.

Conclusion
Lavage of the peritoneal cavity with doses of up to 100,000 collagen digestion units/animal for 30 min is safe and removes connective tissue from the peritoneal cavity.
Gene signatures of circulating breast cancer cell models are a source of novel molecular determinants of metastasis and improve circulating tumor cell detection in patients
Authors: Fina Emanuela , Cleris Loredana , Dugo Matteo , Lecchi Mara , Ciniselli Chiara Maura , Lecis Daniele , Bianchi Giulia Valeria , Verderio Paolo , Daidone Maria Grazia , Cappelletti Vera 
Published: February 2022

Abstract
Background
Progression to stage IV disease remains the main cause of breast cancer-related deaths. Increasing knowledge on the hematogenous phase of metastasis is key for exploiting the entire window of opportunity to interfere with early dissemination and to achieve a more effective disease control. Recent evidence suggests that circulating tumor cells (CTCs) possess diverse adaptive mechanisms to survive in blood and eventually metastasize, encouraging research into CTC-directed therapies.

Methods
On the hypothesis that the distinguishing molecular features of CTCs reveal useful information on metastasis biology and disease outcome, we compared the transcriptome of CTCs, primary tumors, lymph-node and lung metastases of the MDA-MB-231 xenograft model, and assessed the biological role of a panel of selected genes, by in vitro and in vivo functional assays, and their clinical significance in M0 and M+ breast cancer patients.

Results
We found that hematogenous dissemination is governed by a transcriptional program and identified a CTC signature that includes 192 up-regulated genes, mainly related to cell plasticity and adaptation, and 282 down-regulated genes, involved in chromatin remodeling and transcription. Among genes up-regulated in CTCs, FADS3 was found to increases cell membrane fluidity and promote hematogenous diffusion and lung metastasis formation. TFF3 was observed to be associated with a subset of CTCs with epithelial-like features in the experimental model and in a cohort of 44 breast cancer patients, and to play a role in cell migration, invasion and blood-borne dissemination. The analysis of clinical samples with a panel of CTC-specific genes (ADPRHL1, ELF3, FCF1, TFF1 and TFF3) considerably improved CTC detection as compared with epithelial and tumor-associated markers both in M0 and stage IV patients, and CTC kinetics informed disease relapse in the neoadjuvant setting.

Conclusions
Our findings provide evidence on the potential of a CTC-specific molecular profile as source of metastasis-relevant genes in breast cancer experimental models and in patients. Thanks to transcriptome analysis we generated a novel CTC signature in the MDA-MB-231 xenograft model, adding a new piece to the current knowledge on the key players that orchestrate tumor cell hematogenous dissemination and breast cancer metastasis, and expanding the list of CTC-related biomarkers for future validation studies.
A subdermal tagging technique for juvenile sturgeon using a new self-powered acoustic tag
Authors: Liss Stephanie A. , Li Huidong , Deng Zhiqun Daniel 
Published: February 2022

AbstractBackgroundA new technology for a self-powered acoustic tag (SPT) was developed for active tracking of juvenile fish, intended to avoid the typical battery life constraints associated with active telemetry technology. We performed a laboratory study to evaluate a subdermal tagging technique for the SPT and effects of the tag on survival, tag retention, and growth in juvenile white sturgeon (Acipenser transmontanus).ResultsSurvival was associated with tag retention. White sturgeon implanted with the SPT (n = 30) had 93% survival and tag retention by day 28, 67% by day 101, and 38% by day 595 post-tagging. Sturgeon implanted with a passive integrated transponder (PIT) tag only (control group) had 96% survival and tag retention by day 28, and through day 101 post-tagging. Fish in the PIT group were repurposed after day 101, so no comparisons with this group were made at day 595 post-tagging. Specific growth rate (SGR) for fork length was a median of 0.25% day−1by day 28 for the SPT group, which was significantly lower than the PIT group (median: 0.42% day−1;n = 27). The SPT and PIT groups had similar SGR fork length by day 101 post-tagging (0.22 and 0.25% day−1, respectively). SGR weight was also lower for the SPT group compared to the PIT group on day 28 (1.39 and 2.11% day−1, respectively), but the difference again dissipated by day 101 (0.79 and 0.88% day−1, respectively).ConclusionThe tagging technique and placement of the SPT allowed the tag to remain upright along the flank of the sturgeon to ensure maximum battery output of the SPT; however, retention rates of the SPT were not ideal. We provided suggestions to improve the tagging technique. Suggestions included tagging fish that are > 400 mm FL, moving the incision location to extend the cavity and create a pocket for the placement of the SPT, and performing a quantitative wound-healing evaluation. Future studies are therefore recommended to evaluate these suggestions.
Perspectives from law enforcement officers who respond to overdose calls for service and administer naloxone
Authors: Smiley-McDonald Hope M. , Attaway Peyton R. , Richardson Nicholas J. , Davidson Peter J. , Kral Alex H. 
Published: February 2022

Abstract
Background
Many law enforcement agencies across the United States equip their officers with the life-saving drug naloxone to reverse the effects of an opioid overdose. Although officers can be effectively trained to administer naloxone, and hundreds of law enforcement agencies carry naloxone to reverse overdoses, little is known about what happens on scene during an overdose call for service from an officer’s perspective, including what officers perceive their duties and responsibilities to be as the incident evolves.

Methods
The qualitative study examined officers’ experiences with overdose response, their perceived roles, and what happens on scene before, during, and after an overdose incident. In-person interviews were conducted with 17 officers in four diverse law enforcement agencies in the United States between January and May 2020.

Results
Following an overdose, the officers described that overdose victims are required to go to a hospital or they are taken to jail. Officers also described their duties on scene during and after naloxone administration, including searching the belongings of the person who overdosed and seizing any drug paraphernalia.

Conclusion
These findings point to a pressing need for rethinking standard operating procedures for law enforcement in these situations so that the intentions of Good Samaritan Laws are upheld and people get the assistance they need without being deterred from asking for future help.
Good things come to those who mate: analysis of the mating behaviour in the menstruating rodent, Acomys cahirinus
Authors: McKenna Jarrod , Bellofiore Nadia , Temple-Smith Peter 
Published: February 2022

Abstract
Background
The Egyptian spiny mouse (Acomys cahirinus) is the only known rodent to exhibit true, human-like menstruation and postpartum ovulation, and is an important new model for reproductive studies. Spiny mice do not produce a visible copulatory plug, and calculation of gestational age is therefore restricted by the need to use mated postpartum dams. The current inefficient method of monitoring until parturition to provide a subsequent estimate of gestational age increases study duration and costs. This study addressed this issue by comparing the mating behaviour of spiny mice across the menstrual cycle and proposes a more accurate method for staging and pairing animals that provides reliable estimates of gestational age. In experiment 1, mating behaviour was recorded overnight to collect data on mounting, intromission, and ejaculation (n = 5 pairs per stage) in spiny mice paired at menses and at early and late follicular and luteal phases of the menstrual cycle. In experiment 2, female spiny mice were paired at the follicular or luteal phases of the menstrual cycle to determine any effect on the pairing-birth interval (n = 10 pairs).

Results
We report a broad mating window of ~ 3 days during the follicular phase and early luteal phase of spiny mice. Males displayed a discrete ‘foot twitch’ behaviour during intromission and a brief copulatory lock during ejaculation. Litters were delivered after 40–43 days if pairing occurred during the mating window, compared with 46–48 days for spiny mice paired in the late luteal phase. When pairing occurred during the late luteal phase or menses no mating activity was observed during the recording period.

Conclusion
This study clearly demonstrates an effect of the menstrual cycle on mating behaviour and pregnancy in the spiny mouse and provides a reliable and more effective protocol for estimating gestational age without the need for postpartum dams.
External Validation of the 2003 Leibovich Prognostic Score in Patients Randomly Assigned to SORCE, an International Phase III Trial of Adjuvant Sorafenib in Renal Cell Cancer
Authors: Oza Bhavna , Eisen Tim , Frangou Eleni , Stewart Grant D. , Bex Axel , Ritchie Alastair W.S. , Kaplan Rick , Smith Benjamin , Davis Ian D. , Stockler Martin R. , Albiges Laurence , Escudier Bernard , Larkin James , Joniau Steven , Hancock Barry , Hermann Gregers G. , Bellmunt Joaquim , Parmar Mahesh K.B. , Royston Patrick , Meade Angela 
Published: February 2022

PURPOSE The 2003 Leibovich score guides prognostication and selection to adjuvant clinical trials for patients with locally advanced renal cell carcinoma (RCC) after nephrectomy. We provide a robust external validation of the 2003 Leibovich score using contemporary data from SORCE, an international, randomized trial of sorafenib after excision of primary RCC. METHODS Data used to derive the 2003 Leibovich score were compared with contemporary data from SORCE. Discrimination and calibration of the metastasis-free survival outcome were assessed in data from patients with clear-cell RCC, using Cox proportional hazards regression, Kaplan-Meier curves, and calculation of Harrell's c indexes. Secondary analyses involved three important SORCE groups: patients with any non–clear-cell subtype, papillary, and chromophobe carcinomas. RESULTS Four hundred seven recurrences occurred in 982 patients in the Leibovich cohort and 520 recurrences were recorded in 1,445 patients in the primary SORCE cohort. Clear discrimination between intermediate-risk and high-risk SORCE cohorts was shown; hazard ratio 2.74 (95% CI, 2.29 to 3.28), c-index 0.63 (95% CI, 0.61 to 0.65). A hazard ratio of 0.61 (95% CI, 0.53 to 0.70) confirmed poor calibration of the two cohorts. Discrimination was observed in secondary populations, with c-indexes of 0.64 (95% CI, 0.59 to 0.69) for non–clear-cell RCC, 0.63 (95% CI, 0.56 to 0.69) for papillary RCC, and 0.65 (95% CI, 0.55 to 0.76) for chromophobe RCC. CONCLUSION The 2003 Leibovich score discriminates between intermediate-risk and high-risk clear-cell and non–clear-cell RCC groups in contemporary data, supporting its use for risk stratification in adjuvant clinical trials. Over time, metastasis-free survival for patients with locally advanced RCC has improved. Contemporary data from adjuvant RCC trials should be used to improve prognostication for patients with RCC.