bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inequity in access to digital public primary healthcare in Sweden: a cross-sectional study of the effects of urbanicity and socioeconomic status on utilization
Authors: Eriksson Jon , Calling Susanna , Jakobsson Ulf , Wolff Moa , Borgström Bolmsjö Beata , Milos Nymberg Veronica 
Published: April 2024

Abstract
Background
Social and geographical inequity in access to primary healthcare is an ongoing concern in Sweden. Digital care can potentially decrease geographical inequity. This study aimed to evaluate how urbanicity affects the utilization of a public digital primary healthcare service - PHC Online.

Methods
We performed an ecological cross-sectional study of 4,482 PHC Online visits grouped by 83 public primary healthcare centers. Multiple linear regression analysis was performed with PHC Online visits per 1,000 registered patients as the dependent variable and urbanicity (municipalities grouped by number of inhabitants), socioeconomic status (Care Need Index), and morbidity (Adjusted Clinical Groups) per primary healthcare center as independent variables.

Results
Utilization of PHC Online was more common among those of a younger age (median 32 years) and among women (65%). Urbanicity did not affect utilization. Lower socioeconomic status and higher morbidity had negative effects on utilization (B -3.289, p = 0.001, B -7.728, p = 0.045).

Conclusions
Geographical differences based on urbanicity do not seem to affect the utilization of PHC Online. Further studies are needed to clarify a possible association to geographical barriers in access to primary healthcare, specifically accounting for factors associated with urbanicity and distance to physical clinics, and how age and sex affect such an association. Lower utilization of PHC Online in low socioeconomic status and high morbidity populations raises questions on the effect of digital primary care on equitable access to primary healthcare.
Effect of oesophagectomy on lipid profiles in patients with oesophageal cancer combined with hyperlipidaemia: a retrospective study
Authors: Yang Jingrong , Li Yaxin , Huang Jialei , Lai Jiabin , Chen Xiangrui , Xia Wenxuan , Wang Yu 
Published: April 2024

Abstract
Background
Surgery is widely regarded as a pivotal therapeutic approach for treating oesophageal cancer, and clinical observations have revealed that many oesophageal cancer patients also present with concomitant hyperlipidaemia. It is surprising that few studies have been performed to determine how blood lipid levels are affected by oesophageal cancer resection. This research was designed to assess the influence of oesophageal cancer resection on lipid profiles among individuals diagnosed with both oesophageal cancer and hyperlipidaemia.

Methods
A retrospective analysis was carried out on 110 patients with hyperlipidaemia and oesophageal cancer who had undergone oesophagectomy at the 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army. Preoperative and postoperative serological data were collected at seven-, thirty-, sixty-day-, and one-year-long intervals. Changes in lipid levels were compared, the remission of various types of hyperlipidaemia was statistically assessed, and Pearson correlation was used to analyse the association between lipid changes and preoperative body weight. The research sought to assess the reduction in body weight and the proportion of body weight lost one year following surgery.

Results
Noteworthy decreases were observed in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, with TC decreasing from 6.20 mmol/L to 5.20 mmol/L, TG decreasing from 1.40 mmol/L to 1.20 mmol/L, and LDL decreasing from 4.50 mmol/L to 3.30 mmol/L. Conversely, there was a notable increase in high-density lipoprotein (HDL) levels, which increased from 1.20 mmol/L to 1.40 mmol/L (P < 0.05) compared to the preoperative levels. Notably, the remission rates for mixed hyperlipidaemia (60.9%) and high cholesterol (60.0%) were considerably greater than those for high triglycerides (16.2%). Alterations in TC at one year postoperatively correlated with preoperative weight and weight loss (r = 0.315, -0.216); changes in TG correlated with preoperative weight, percentage of total weight loss (TWL%), and weight reduction (r = -0.295, -0.246, 0.320); and changes in LDL correlated with preoperative weight, TWL%, and weight loss (r = 0.251, 0.186, and -0.207). Changes in non-high-density lipoprotein(non-HDL) were linked to preoperative weight (r = 0.300), and changes in TG/HDL were correlated with preoperative weight and TWL% (r = -0.424, -0.251).

Conclusions
Oesophagectomy significantly improved lipid profiles in oesophageal cancer patients, potentially leading to a reduction in overall cardiovascular risk.
Characteristics and outcomes of the drug patent linkage system in China
Authors: Yao Xue-Fang 
Published: April 2024

Abstract
Background
On July 4, 2021, China officially introduced the drug patent linkage system, which has made more localized adjustments than have similar systems in the US and South Korea. This study describes the characteristics and outcomes of China’s patent linkage system.

Methods
For this study, we used the database of China’s patent information registration platform for marketed drugs to capture all listed patents and patent certifications from June 25, 2021, to June 30, 2023. We used descriptive statistics for the above data to assess the impact of patent linkage on branded drug manufacturers, generic drug manufacturers, and the public’s access to medicines.

Results
During the study period, the patents of 632 branded drugs were listed, and 5058 ANDAs submitted patent certifications to the Registration Platform. Of these 632 branded drugs, 462 (73.1%) drugs were approved before the year of patent registration, and the average number of listed patents per drug was 1.8, with a standard deviation of 1.4. However, of these 5058 ANDAs, P1 certifications accounted for 85.1%, and P3 and P4 certifications accounted for 16% combined. In addition, according to the detailed statistics of P2 certifications, we found that the proportion of patent invalidation cases was 46.4%. The remaining validity of the patents corresponding to P3 certifications was longer, with a median value of 17 months, and the IQR was 10-30.75, ranging from − 2 to 204 months.

Conclusions
China’s patent linkage aims to promote the balance of multiple interests —innovation, imitation and public health—and has its own system characteristics. Patent listing and patent certification are the key indicators reflecting the implementation effect of the system. From the perspective of system outcomes, ANDAs have been connected to the patent linkage system in an orderly manner, but the growth of patent challenges is not obvious. Moreover, manufacturers of foreign branded drugs that have not yet entered the Chinese market need to pay more attention to the role of patent listing.
Prevalence of obesity and associated health risks in soldiers of the German Armed Forces
Authors: Scheit Lorenz , Schröder Jan , Will Selina , Reer Rüdiger , Hoffmann Manuela Andrea 
Published: April 2024

Abstract
Background
Obesity rates are rising in the armed forces of Western democratic countries, impacting military readiness and health. This highlights the need for preventive health risk assessments and countermeasures.

Methods
Using mandatory health examination data from 2018 to 2022, we analyzed the prevalence of obesity, health risks, and associated specific military risk factors (rank and unit) in 43,214 soldiers of the German Armed Forces. Statistical methods included χ2 contingencies and binary logistic regressions.

Results
The prevalence of obesity (BMI ≥ 30) was 18.0%. Male soldiers (OR = 3.776) and those with an officer’s rank (OR = 1.244) had an increased chance for obesity. Serving in a combat unit reduced the chance of being obese (OR = .886). Considering BMI and waist circumference, 2.4% of the total sample faced extremely high cardiovascular and metabolic health risks, while 11.0% and 11.6% had very high or high health risks, respectively.

Conclusions
Our data underscore the importance of targeting obesity-related health risk factors in soldiers to ensure their well-being and deployment readiness.
Circ_0044235 regulates the development of osteoarthritis by the modulation of miR-375/PIK3R3 axis
Authors: Qian Wenjie , Mei Kai , Zhu Lei , Chu Ying , Lv Jinpeng , Yun Changjun 
Published: April 2024

Abstract
Background
Circular RNAs (circRNAs) play an important role in osteoarthritis (OA). However, the role of circRNA in OA is still unclear. Here, we explored the role and mechanism of circ_0044235 in OA.

Methods
CHON-001 cells were treated with IL-1β to establish OA model in vitro. The levels of circ_0044235, miR-375 and phosphoinositide 3-kinase (PI3K) regulatory subunit 3 (PIK3R3) were detected by quantitative real-time PCR. Cell count kit-8 assay and flow cytometry assay were used to detect cell viability and apoptosis. The concentrations of inflammation factors were determined by enzyme-linked immunosorbent assay. Western blot was used to detect protein levels. The interaction between miR-375 and circ_0044235 or PIK3R3 was analyzed by dual-luciferase reporter assay and RNA immunoprecipitation assay.

Results
Circ_0044235 was significantly decreased in OA cartilage tissue and IL-1β-treated CHON-001 cells. Overexpression of circ_0044235 promoted IL-1β-stimulated CHON-001 cell viability and inhibited apoptosis, inflammation, and extracellular matrix (ECM) degradation. In mechanism analysis, circ_0044235 could act as a sponge for miR-375 and positively regulate PIK3R3 expression. In addition, miR-375 ameliorated the effect of circ_0044235 overexpression on IL-1β-mediated CHON-001 cells injury. In addition, miR-375 inhibition mitigated IL-1β-induced CHON-001 cell injury, while PIK3R3 silencing restored the effect.

Conclusion
Circ_0044235 knockdown alleviated IL-1β-induced chondrocytes injury by regulating miR-375/PIK3R3 axis, confirming that circ_0044235 might be a potential target for OA treatment.
Meta-analysis of the efficacy and safety of OLIF and TLIF in the treatment of degenerative lumbar spondylolisthesis
Authors: Shi Jing , Wu Han , Li Fenyao , Zheng Jinpeng , Cao Ping , Hu Bing 
Published: April 2024

Abstract
Objective
To systematically evaluate the difference in clinical efficacy between two surgical approaches, oblique lateral approach and intervertebral foraminal approach, in the treatment of degenerative lumbar spondylolisthesis.

Methods
English databases, including PubMed, Cochrane, Embase, and Web of Science, were systematically searched using keywords such as "oblique lumbar interbody fusion" and "transforaminal lumbar interbody fusion." Concurrently, Chinese databases, including CNKI, WanFang data, VIP, and CBM, were also queried using corresponding Chinese terms. The search spanned from January 2014 to February 2024, focusing on published studies in both Chinese and English that compared the clinical efficacy of OLIF and TLIF. The literature screening was conducted by reviewing titles, abstracts, and full texts. Literature meeting the inclusion criteria underwent quality assessment, and relevant data were extracted. Statistical analysis and a meta-analysis of the observational data for both surgical groups were performed using Excel and RevMan 5.4 software. Findings revealed a total of 14 studies meeting the inclusion criteria, encompassing 877 patients. Of these, 414 patients were in the OLIF group, while 463 were in the TLIF group. Meta-analysis of the statistical data revealed that compared to TLIF, OLIF had a shorter average surgical duration (P < 0.05), reduced intraoperative bleeding (P < 0.05), shorter average hospital stay (P < 0.05), better improvement in postoperative VAS scores (P < 0.05), superior enhancement in postoperative ODI scores (P < 0.05), more effective restoration of disc height (P < 0.05), and better correction of lumbar lordosis (P < 0.05). However, there were no significant differences between OLIF and TLIF in terms of the incidence of surgical complications (P > 0.05) and fusion rates (P > 0.05).

Conclusion
When treating degenerative lumbar spondylolisthesis, OLIF demonstrates significant advantages over TLIF in terms of shorter surgical duration, reduced intraoperative bleeding, shorter hospital stay, superior improvement in postoperative VAS and ODI scores, better restoration of disc height, and more effective correction of lumbar lordosis.
Abnormal performance of peroral endoscopic myotomy (POEM): a case misdiagnosed as achalasia of cardia
Authors: Yu Wen-Quan , Gao Hui-Jiang , Zhai Li-Xue , Wei Yu-Cheng 
Published: April 2024

Abstract
Background
Pseudoachalasia is a rare disease that behaves similarly to achalasia (AC), making it sometimes difficult to differentiate.

Case presentation
We report a case of 49-year-old male with adenocarcinoma of the gastroesophageal junction misdiagnosed as achalasia. No obvious abnormalities were found in his initial examinations including upper digestive endoscopy, upper gastrointestinal imaging and chest computed tomography (CT). During the subsequent introduced-peroral endoscopic myotomy (POEM), it was found that the mucosal layer and the muscular layer had severe adhesion, which did not receive much attention, delayed the clear diagnosis and effect treatment, and ultimately led to a poor prognosis for the patient.

Conclusions
This case suggests that when patients with AC found mucosal and muscular adhesions during POEM surgery, the possibility should be considered that the lesion may be caused by a malignant lesion.
Neoadjuvant immunochemotherapy for pulmonary large-cell neuroendocrine carcinoma: case report
Authors: Xu Chang , Zhao Guangyin , Zhang Hongyu , Ge Di , Gu Jie 
Published: April 2024

Abstract
Background
Pulmonary large-cell neuroendocrine carcinoma (pLCNEC) represents a rare malignancy characterized by its aggressive behavior and a notably high recurrence rate. Remarkably, there is currently no established standard treatment protocol for this condition.

Case description
In this report, we present an intriguing case of pLCNEC diagnosed at clinical-stage IIB. This case involves a 64-year-old man with a smoking history spanning four decades. In our approach, we initiated a course of neoadjuvant chemotherapy in combination with pembrolizumab, administered for two cycles prior to surgical resection. This innovative treatment strategy resulted in a significant pathological response, culminating in a major pathological remission (MPR). As of the time of composing this report, the patient has been diligently monitored for 39 months post-surgery, exhibiting no indications of recurrence, and has demonstrated exceptional tolerance to the entire treatment regimen.

Conclusions
We have first reported a clinically successful case of neoadjuvant combination chemotherapy with pembrolizumab in the treatment of pLCNEC. This case offers promising clinical insights and suggests that this therapeutic approach could be a viable option for managing pLCNEC.
Successful Implantation of Rapid Deployment Aortic Valve after TAVR Explantation
Authors: Yanagino Yusuke , Kawamoto Naonori , Kainuma Satoshi , Tadokoro Naoki , Kakuta Takashi , Ikuta Ayumi , Tonai Kohei , Fujita Tomoyuki , Fukushima Satsuki 
Published: April 2024

Abstract
Background
Transcatheter aortic valve replacement (TAVR) has become widely used in recent years, However, there is also an increasing need for removal of TAVR valves due to prosthetic valve dysfunction (PVD) and the development of infective endocarditis. Surgical aortic valve replacement (AVR) for these patients is risky due to the original patient background and anatomic conditions. Intuity rapid deployment aortic valve (Edwards Lifesciences, Irvine, CA) replacement would be useful for such high risk patients to prevent longer cardiac arrest time and obtain good hemodynamic results. However, there are few reports which present Intuity valve replacement after TAVR explantation. Herein, We report two cases in which we have achieved good hemodynamics with shorter cardiac arrest times by using a rapid deployment valve after TAVR explantation.

Case presentation
We present 2 cases of successful implantation of the Intuity rapid deployment valve after TAVR explantation. The 84- and 88-year-old female patients had previously received TAVR for severe aortic stenosis with SAPIEN XT (Edwards Lifesciences, Irvine, CA) and developed PVD during follow-up. The TAVR valve was removed carefully, then an Intuity valve was implanted with cardiac arrest times of 69 and 41 min. Both patients had good echocardiographic results with effective orifice area of 2.0 cm2 and 1.2 cm2 and mean trans-aortic plessure gradient of 9 mmHg and 15 mmHg respectively without aortic regurgitation. They were discharged without major complications.

Conclusions
Surgical AVR using a rapid deployment valve is a useful alternative to sutured AVR after TAVR valve explantation. It allows for shorter cardiac arrest times and better postoperative hemodynamics without major complication.
Triple-induction treatment for locally advanced non-small cell lung cancer: a case report of pathological complete response
Authors: Werner Raphael S. , Lauk Olivia , Tscherry Georg , Curioni-Fontecedro Alessandra , Höller Sylvia , Opitz Isabelle 
Published: April 2024

Abstract
Background
In patients with resectable stage III non-small cell lung cancer (NSCLC), induction chemoimmunotherapy followed by surgical resection has shown unprecedented rates of pathological response and event-free survival. However, a triple-induction including radiochemotherapy and immunotherapy followed by surgical resection has not been routinely established in clinical practice.

Case presentation
We report the case of a 47-year-old patient with stage IIIA NSCLC who was treated in a combined concept including induction concurrent radiochemotherapy, followed by 4 cycles of pembrolizumab and subsequent intrapericardial left-sided pneumonectomy. Histological analysis revealed a pathological complete response.

Conclusions
The case demonstrates that the combination of neoadjuvant chemo-, radio- and immunotherapy in advanced NSCLC may lead to a relevant down-staging and may enable a R0-resection of a borderline resectable tumor. However, the combination of four different treatment modalities requires resilience and a good performance status. A triple induction treatment may be a promising option for selected patients with locally advanced NSCLC and good performance status.
A case of severe benzalkonium chloride intoxication in a cat
Authors: Rubini Silva , Rubini Roberto , Bertocchi Silvia , Zordan Silvia , Magri Alice , Barsi Filippo , Sampieri Maria , Locatelli Carlo Alessandro , Baldini Erika , Manfredini Stefano , Vertuani Silvia 
Published: April 2024

Abstract
Background
Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC), that can be found in a wide variety of household products–from disinfectants to medicaments and home fragrances–but also professional products. In pets, cats have long been reported as more sensitive than dogs to QACs; in fact, signs of irritation such as oral ulcerations, stomatitis and pharyngitis can be observed after contact with concentrations of 2% or lower. In a review of 245 cases of BAC exposure in cats, reported by the Veterinary Poisons Information Service (United Kingdom) only 1.2% of the cases died or were euthanized. Nevertheless, BAC toxidromes in cats can result in transitory CNS and respiratory distress, as well as severe mucosal and cutaneous lesions. Currently, only a few reports are available concerning BAC poisoning in this species.

Case presentation
A 4 month-old kitten presented with severe glossitis, lameness in the hindlimbs and episodes of vomiting and diarrhoea. The cause was unknown until the owners reported use of a BAC-containing mould remover (5%) 4 days later. The patient developed severe oral burns requiring a pharyngeal tube for feeding and severe cutaneous chemical burns. The kitten was managed with supportive therapy and required hospitalization for 10 days. The symptoms disappeared completely 3 weeks after exposure.

Conclusions
BAC is a very common compound contained in several household and professional products but, to the best of our knowledge, no previous case had been reported in Italy. We hope that this report will help raise awareness on the hazards of BAC products for cats in both domestic and work contexts.
TERT RNAscope analysis of sub-centimetric papillary thyroid carcinomas and synchronous lymph node metastases
Authors: Eich Marie-Lisa , Jeske Wiebke , Zenz Uschi , Chiapponi Costanza , Alidousty Christina , Merkelbach-Bruse Sabine , Büttner Reinhard , Schultheis Anne M. 
Published: April 2024

Abstract
Background
Sub-centrimetric papillary thyroid carcinomas usually have a good prognosis with a cancer specific survival of > 99%, however in up to 65% of patients, lymph node metastases can be observed. Molecular alterations in BRAF, TERT and TP53 are associated with worse clinicopathological outcome in patients with papillary thyroid carcinoma.

Material and methods
Twenty-two cases of papillary thyroid carcinomas measuring ≤ 1 cm with synchronous lymph node metastases were examined regarding morphological patterns and immunohistochemical status of p53, Ki-67, and BRAF V600E status. TERT RNA expression in lymph node metastases were evaluated by RNAScope®.

Results
Morphological patterns were heterogeneous in both primary tumors and lymph node metastases. Proliferation indices measured by Ki-67 were low. Both primary and lymph node metastases were wild type for p53 by immunohistochemical analysis. No lymph node metastasis showed TERT expression by RNAScope®.

Conclusions
Our data indicate that TERT expression is not involved in the development early lymph node metastasis in patients with sub-centimetric PTC.
Selective epigenetic alterations in RNF43 in pancreatic exocrine cells from high-fat-diet-induced obese mice; implications for pancreatic cancer
Authors: Araki Tomoyuki , Miwa Naofumi 
Published: April 2024

Abstract
Objective
Pancreatic cancer (PC) originates and progresses with genetic mutations in various oncogenes and suppressor genes, notably KRAS, CDKN2A, TP53, and SMAD4, prevalent across diverse PC cells. In addition to genetic mutations/deletions, persistent exposure to high-risk factors, including obesity, induces whole-genome scale epigenetic alterations contributing to malignancy. However, the impact of obesity on DNA methylation in the presymptomatic stage, particularly in genes prone to PC mutation, remains uncharacterized.

Results
We analyzed the methylation levels of 197 loci in six genes (KRAS, CDKN2A, TP53, SMAD4, GNAS and RNF43) using Illumina Mouse Methylation BeadChip array (280 K) data from pancreatic exocrine cells obtained from high-fat-diet (HFD) induced obese mice. Results revealed no significant differences in methylation levels in loci between HFD- and normal-fat-diet (NFD)-fed mice, except for RNF43, a negative regulator of Wnt signaling, which showed hypermethylation in three loci. These findings indicate that, in mouse pancreatic exocrine cells, high-fat dietary obesity induced aberrant DNA methylation in RNF43 but not in other frequently mutated PC-related genes.