bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of 30% vs. 60% inspired oxygen fraction during mechanical ventilation on postoperative atelectasis: a randomised controlled trial
Authors: Jiang Zhaoshun , Liu Songbin , Wang Lan , Li Wanling , Li Cheng , Lang Feifei , Li Ruoxi , Zhou Yue , Wu Jiajun , Cai Yuxi , Xu Wen , Chen Zhen , Bao Zhijun , Li Ming , Gu Weidong
Published: August 2023

Background

There is the ongoing debate over the effect of inspired oxygen fraction (FiO2) during mechanical ventilation on postoperative atelectasis. We aimed to compare the effects of low (30%) and moderate (60%) FiO2 on postoperative atelectasis. The hypothesis of the study was that 30% FiO2 during mechanical ventilation could reduce postoperative atelectasis volume compared with 60% FiO2.

Methods

We performed a randomized controlled trial with 120 patients. Subjects were randomly assigned to receive 30% or 60% FiO2 during mechanical ventilation in a 1:1 ratio. The primary outcome was the percentage of postoperative atelectasis volume in the total lung measured using chest CT within 30 min after extubation. The secondary outcomes included different aeration region volumes, incidence of clinically significant atelectasis, and oxygenation index.

Results

In total, 113 subjects completed the trial, including 55 and 58 subjects in the 30% and 60% FiO2 groups, respectively. The percentage of the postoperative atelectasis volume in the 30% FiO2 group did not differ from that in the 60% FiO2 group. Furthermore, there was no significant difference in the atelectasis volume between the two groups after the missing data were imputed by multiple imputation. Additionally, there were no significant differences in the volumes of the over-aeration, normal-aeration, and poor-aeration regions between the groups. No significant differences in the incidence of clinically significant atelectasis or oxygenation index at the end of surgery were observed between the groups.

Conclusions

Compared with 60% FiO2, the use of 30% FiO2 during mechanical ventilation does not reduce the postoperative atelectasis volume.

Trial registration

Chinese Clinical Trial Registry (http://www.chictr.org.cn). Identifier: ChiCTR1900021635. Date: 2 March 2019. Principal invetigator: Weidong Gu.
BYL719 reverses gefitinib-resistance induced by PI3K/AKT activation in non-small cell lung cancer cells
Authors: Yu Yaya , Xiao Zhenzhen , Lei Chenjing , Ma Changju , Ding Lina , Tang Qing , He Yihan , Chen Yadong , Chang Xuesong , Zhu Yanjuan , Zhang Haibo
Published: August 2023

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation often obtain de novo resistance or develop secondary resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), which restricts the clinical benefit for the patients. The activation of phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway is one of the most important mechanisms for the EGFR-TKIs resistance beyond T790M mutation. There are currently no drugs simultaneously targeting EGFR and PI3K signal pathways, and combination of these two pathway inhibitors may be a possible strategy to reverse theses resistances. To test whether this combinational strategy works, we investigated the therapeutic effects and mechanisms of combining BYL719, a PI3Kα inhibitor, with gefitinib, an EGFR-TKI inhibitor in EGFR-TKIs resistance NSCLC models induced by PI3K/AKT activation. Our results demonstrated that PIK3CA mutated cells showed increased growth rate and less sensitive or even resistant to gefitinib, associated with increased PI3K/AKT expression. The combination of BYL719 and gefitinib resulted in synergistic effect compared with the single agents alone in EGFR-mutated NSCLC cells with PI3K/AKT activation. The inhibition of AKT phosphorylation by BYL719 increased the antitumor efficacy of gefitinib in these cell lines. Moreover, the combined effect and mechanism of gefitinib and BYL719 were also confirmed in the NSCLC cells and patient-derived organoids under 3D culture condition, as well as in vivo. Taken together, the data indicate that PIK3CA mutation induces more aggressive growth and gefitinib resistance in NSCLC cells, and the combination treatment with gefitinib and BYL719 is a promising therapeutic approach to overcoming EGFR-TKIs resistance induced by PI3K/AKT activation.
A novel missense variant expands the phenotype and genotype of PAX6-associated foveal hypoplasia accompanied by various manifestations of anterior segment dysgenesis
Authors: Yu Yanping , Jia Hongyan , Ma Qian , Zhang Ranran , Jiao Yonghong
Published: August 2023

Background

According to previous reports, PAX6-associated foveal hypoplasia (FH) could usually be accompanied by various anterior segment anomalies including variable iris changes. This study aims to exhibit unusual phenotypes of a novel missense variant of PAX6 from a Chinese pedigree.

Methods

Ophthalmic examinations including slit-lamp biomicroscopy, gonioscopy, ophthalmic ultrasound, ultrasonic biomicroscopy, optical coherence tomography, wide-field fundus imaging, and visual field test were performed to evaluate the clinical manifestations. Whole-exome sequencing (WES) and bioinformatics analysis were conducted in eight members from this pedigree to identify the causative mutation.

Results

WES revealed a novel heterozygous substitution of PAX6 (NM_000280.5:c.157G > A, p.(Val53Met) (chr11:31823309 C > T, hg19)), which cosegregated with the phenotype of this pedigree. All the three patients (a pair of fraternal twins and their mother) exhibited bilateral FH and anterior segment dysgenesis (ASD) including microcornea, sclerocornea, obvious symmetrical corectopia, iris stromal dysplasia, goniodysgenesis, and abnormal distribution of fundus blood vessels. The girl of the fraternal twins also demonstrated bilateral temporal deviation of lenses and abnormal tissue membrane connecting anterior chamber angle and lens anterior capsule in the right eye. The mother additionally showed apparent cataract bilaterally and cupping of the optic disc in her left eye.

Conclusion

A novel missense variant in PAX6 gene was detected in a Chinese pedigree demonstrating bilateral FH and ASD. It is really distinctive that the ASD involves almost all parts of the anterior segment, and bilateral symmetrical corectopia is the most perceptible sign. This study expands the phenotypic and genotypic spectrum of PAX6-associated ocular diseases, and facilitates the understanding of the crucial role that PAX6 plays in the development of the eye. Meanwhile, PAX6 could be considered as a candidate pathogenic gene of bilateral symmetrical corectopia.
Early neurological and motor function in infants born moderate to late preterm or small for gestational age at term: a prospective cohort study
Authors: Paulsen Henriette , Ljungblad Ulf Wike , Riiser Kirsti , Evensen Kari Anne I.
Published: August 2023

Background

There are inconsistent findings regarding neurological and motor development in infants born moderate to late preterm and infants born small for gestational age at term. The primary aim of this study was to compare neurological and motor function between preterm, term SGA and term AGA infants aged three to seven months corrected age using several common assessment tools. The secondary aim was to investigate their motor function at two years.

Methods

In this prospective cohort study, we included 43 infants born moderate to late preterm with gestational age 32–36 + 6 weeks, 39 infants born small for gestational age (SGA) at term with a birthweight ≤ 10th centile for gestational age, and 170 infants born at term with appropriate weight for gestational age (AGA). Neurological and motor function were assessed once in infancy between three to seven months corrected age by using four standardised assessment tools: Hammersmith Infant Neurological Examination (HINE), Test of Infant Motor Performance, General Movements Assessment and Alberta Infant Motor Scale. The Ages and Stages Questionnaire (ASQ-2) was used at two years.

Results

At three to seven months corrected age, mean age-corrected HINE scores were 61.8 (95% confidence interval (CI): 60.5 to 63.1) in the preterm group compared with 63.3 (95% CI: 62.6 to 63.9) in the term AGA group. Preterm infants had 5.8 (95% CI: 2.4 to 15.4) higher odds for HINE scores < 10th percentile. The other test scores did not differ between the groups. At two years, the preterm group had 17 (95% CI: 1.9 to 160) higher odds for gross motor scores below cut-off on ASQ-2 compared with the term AGA group.

Conclusions

The present study found subtle differences in neurological function between preterm and term AGA infants in infancy. At two years, preterm children had poorer gross motor function. The findings indicate that moderate prematurity in otherwise healthy infants pose a risk for neurological deficits not only during the first year, but also at two years of age when compared with term AGA children.
The Bergen 4-day treatment for panic disorder: adapting to COVID-19 restrictions with a hybrid approach of face-to-face and videoconference modalities
Authors: Hjelle Kay Morten , Eide Thorstein Olsen , Thorsen Anders Lillevik , Kvale Gerd , Hagen Kristen , Snorrason Ivar , Björgvinsson Thröstur , Hansen Bjarne
Published: August 2023

Background

The Bergen 4-day treatment (B4DT) is a concentrated exposure-based therapy that has been shown to be effective in the treatment of anxiety disorders. The current study sought to examine the effectiveness of B4DT for panic disorder (PD), when delivered with a combination of face-to-face sessions and videoconferencing.

Methods

Treatment was delivered to 50 patients from April 2020 to May 2021. Because of regulations during the pandemic, a significant portion of the treatment was conducted via videoconference. The primary outcome measure was the clinician-rated Panic Disorder Severity Scale (PDSS), and secondary measures included patient-rated symptoms of panic disorder, agoraphobia, generalized anxiety, depression, and treatment satisfaction. Changes in symptom levels over time were estimated using multilevel models.

Results

Patients showed a significant reduction in clinician-rated symptoms of panic disorder (Measured by PDSS) from before treatment to post treatment (d = 2.18) and 3-month follow-up (d = 2.01). At three months follow-up 62% of patients were classified as in remission, while 70% reported a clinically significant response. We also found a reduction in symptoms of depression and generalized anxiety, and the patients reported high satisfaction with the treatment.

Conclusion

The current study suggests that B4DT delivered in a combination of videoconference and face-to-face meetings may be a useful treatment approach. As the study is uncontrolled, future studies should also include more strictly designed investigations.
Risk factors for neck pain in college students: a systematic review and meta-analysis
Authors: Gao Yifang , Chen Zhiming , Chen Shaoqing , Wang Shizhong , Lin Jianping
Published: August 2023

Background

During the COVID-19 epidemic, the prevalence of neck pain among college students has increased due to the shift from offline to online learning and increasing academic and employment pressures. Therefore, this systematic review aimed to identify the personal, occupational, and psychological factors associated with the development of neck pain to promote the development of preventive strategies and early intervention treatment.

Methods

Seven electronic databases were searched from inception to December 2022 for cross-sectional studies, cohort studies, case­­-­control studies, and randomized controlled trials (RCTs) on neck pain. The quality of the selected studies were assessed by American Agency for Healthcare Research and Quality (AHRQ) or the Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the effects of the included risk factors on neck pain.

Results

Thirty studies were included, including 18,395 participants. And a total of 33 potentially associated risk factors were identified. Ultimately, 11 risk factors were included in the meta-analysis after assessing, and all results were statistically significant (P < 0.05). The factors supported by strong evidence mainly include the improper use of the pillow (OR = 2.20, 95% CI: 1.39 to 3.48), lack of exercise (OR = 1.88, 95% CI: 1.53 to 2.30), improper sitting posture (OR = 1.97, 95% CI: 1.39 to 2.78), history of neck and shoulder trauma (OR = 2.32, 95% CI: 1.79 to 3.01), senior grade (OR = 2.86, 95% CI: 2.07 to 3.95), staying up late (OR = 1.80, 95% CI: 1.35 to 2.41), long-time electronic product usage daily (OR = 1.53, 95% CI: 1.33 to 1.76), long-time to bow head (OR = 2.04, 95% CI: 1.58 to 2.64), and emotional problems (OR = 2.09; 95% CI: 1.66  to 2.63). Risk factors supported by moderate evidence were high stress (OR = 1.61, 95% CI: 1.02 to 2.52) and female gender (OR = 1.69, 95% CI: 1.52 to 1.87).

Conclusion

This study obtained 11 main risk factors affecting college students neck pain, including improper use of the pillow, lack of exercise, improper sitting posture, history of neck and shoulder trauma, senior grade, staying up late, long-term electronic product usage daily, long time to bow head, high stress, emotional problems and female gender.
Correlations between moral courage, moral sensitivity, and ethical decision-making by nurse interns: a cross-sectional study
Authors: Luo Zongting , Tao Lan , Wang Carol Chunfeng , Zheng Nan , Ma Xiaolin , Quan Yi , Zhou Jian , Zeng Zhen , Chen Lijuan , Chang Yue
Published: August 2023

Background

Clinical decision-making involves ethical issues that become more and more complex. Nurse interns must be more skilled in making rational and timely decisions when facing ethical dilemmas. The contributing factors and their relationships that challenge ethical decision-making among nurse interns must be fully understood, as this level of knowledge can support the development of strategies and interventions that improve the ethical decision-making ability of nurse interns.

Objective

This study examined the relationships between moral courage, moral sensitivity, and ethical decision-making by nurse interns. In addition, we investigated whether moral sensitivity mediates the relationship between moral courage and ethical decision-making.

Design

A descriptive cross-sectional study using an online questionnaire.

Setting

The study sampled nurse interns from Class iii Grade A general hospitals in Sichuan Province, China.

Participants

A convenience sampling method was used to select 1334 nurse interns from March 2022 to May 2022.

Methods

A general information questionnaire, the Nurses’ Moral Courage Scale (NMCS), the Chinese Moral Sensitivity Questionnaire (MSQ), and the Judgement About Nursing Decision (JAND) were used for data collection. Data was processed and analysed using SPSS 26.0 and Amos 28.0. Data analysis included descriptive statistics, Pearson correlation analysis, and structural equation modelling.

Results

Moral courage was found to be positively correlated with ethical decision-making (P < 0.01). Moral sensitivity was also positively correlated with ethical decision-making (P < 0.01) and had a mediating effect on the relationship between moral courage and ethical decision-making (P < 0.01).

Conclusions

The moral courage and moral sensitivity of nurse interns are positively correlated with ethical decision-making ability. Moral sensitivity significantly mediates the relationship between moral courage and ethical decision-making ability. The knowledge gained from this study can inform educational strategies and interventions in supporting the development of nurse interns’ ethical decision-making ability.
Effect of season on the dynamics of cat sperm DNA fragmentation
Authors: Luño Victoria , Martínez Felisa , Muñoz Andrea , Gil Lydia
Published: August 2023

Background

Feline species undergo reproductive seasonality; thus, sperm characteristics, such as DNA integrity, can be affected by the photoperiod. This study was conducted to determine the effect of seasonal changes on sperm quality and on the dynamics of sperm DNA fragmentation. Epididymal spermatozoa were collected from 36 tomcats subjected to bilateral orchiectomy during breeding (BS) and non-breeding (NBS) seasons. Sperm samples were obtained by cutting the cauda epididymis and assessed for sperm motility, concentration, acrosome integrity, plasma membrane integrity and sperm morphology. Sperm DNA fragmentation was evaluated by the sperm chromatin dispersion test after 0, 6, and 24 h of incubation at 37 °C.

Results

The total sperm motility and plasma membrane integrity values were greater during the BS, while the percentages of abnormal sperm and head defects were lesser (p < 0.05). No significant differences in DNA fragmentation were found between seasons after sperm collection. DNA damage was greater after 24 h of incubation at 37 °C in both seasons, although the percentage of spermatozoa with fragmented DNA was significantly lesser in the BS than in the NBS at 24 h (p < 0.05).

Conclusions

The study suggests seasonal changes in some of the quality parameters of cat sperm. DNA fragmentation dynamics were affected by the time of incubation and reproductive season; therefore, this technique might be used as an additional tool to test the potential fertility of semen samples used in feline-assisted reproduction.
Health needs of migrant female head porters in Ghana: evidence from the Greater Accra and Greater Kumasi Metropolitan areas
Authors: Opuni Rhanda Kyerewaa , Adei Dina , Mensah Anthony Acquah , Adamtey Ronald , Agyemang-Duah Williams
Published: August 2023

Background

In low-and middle-income countries, migrants are confronted with health needs which affect the promotion of their well-being and healthy lives. However, not much is known about the health needs of migrant female head porters (Kayayei) in Ghana. This study assesses the health needs of migrant female head porters in the Greater Kumasi Metropolitan Area (GKMA) and Greater Accra Metropolitan Area (GAMA).

Methods

The study adopted a convergent mixed methods design where both qualitative and quantitative data were used. A representative sample size of 470 migrant female head porters was used for the study.

Results

The study revealed that ante-natal care, post-natal care, treatment of malaria, treatment of diarrhoea diseases, mental health, sexual health, and cervical cancer were health needs of migrant female head porters. The findings showed that participants from the GAMA significantly have greater cervical cancer needs (71.6% vrs 67.1%, p = 0.001) compared to those from the GKMA. Kayeyei from the GKMA significantly have greater mental health needs than those from the GAMA (84.6% vrs 79.2%, p = 0.031). Also, Kayeyei from the GKMA significantly have higher attendance of post-natal care compared to those from the GAMA (99.4% vrs 96.2%, p = 0.013).

Conclusion

The findings underscore differential health needs across geographical localities. Based on the findings of the study, specific health needs such as ante-natal care and post-natal care should be included in any health programmes and policies that aim at addressing health needs of migrant female head porters in the two metropolitan areas of Ghana.
Terebra steering in chalcidoid wasps
Authors: Eggs Benjamin , Fischer Stefan , Csader Michael , Mikó István , Rack Alexander , Betz Oliver
Published: August 2023

Various chalcidoid wasps can actively steer their terebra (= ovipositor shaft) in diverse directions, despite the lack of terebral intrinsic musculature. To investigate the mechanisms of these bending and rotational movements, we combined microscopical and microtomographical techniques, together with videography, to analyse the musculoskeletal ovipositor system of the ectoparasitoid pteromalid wasp Lariophagus distinguendus (Förster, 1841) and the employment of its terebra during oviposition. The ovipositor consists of three pairs of valvulae, two pairs of valvifers and the female T9 (9th abdominal tergum). The paired 1st and the 2nd valvulae are interlocked via the olistheter system, which allows the three parts to slide longitudinally relative to each other, and form the terebra. The various ovipositor movements are actuated by a set of nine paired muscles, three of which (i.e. 1st valvifer-genital membrane muscle, ventral 2nd valvifer-venom gland reservoir muscle, T9-genital membrane muscle) are described here for the first time in chalcidoids. The anterior and posterior 2nd valvifer-2nd valvula muscles are adapted in function. (1) In the active probing position, they enable the wasps to pull the base of each of the longitudinally split and asymmetrically overlapping halves of the 2nd valvula that are fused at the apex dorsally, thus enabling lateral bending of the terebra. Concurrently, the 1st valvulae can be pro- and retracted regardless of this bending. (2) These muscles can also rotate the 2nd valvula and therefore the whole terebra at the basal articulation, allowing bending in various directions. The position of the terebra is anchored at the puncture site in hard substrates (in which drilling is extremely energy- and time-consuming). A freely steerable terebra increases the chance of contacting a potential host within a concealed cavity. The evolution of the ability actively to steer the terebra can be considered a key innovation that has putatively contributed to the acquisition of new hosts to a parasitoid’s host range. Such shifts in host exploitation, each followed by rapid radiations, have probably aided the evolutionary success of Chalcidoidea (with more than 500,000 species estimated).
Epstein Barr virus infection in tree shrews alters the composition of gut microbiota and metabolome profile
Authors: Xia Wei , Liu Lei , Shi Nan , Zhang Chaoyin , Tang Anzhou , He Guangyao
Published: August 2023

Background

Epstein-Barr virus (EBV) infection is a major global threat; its manifestations range from the absence of symptoms to multiorgan malignancies and various gastrointestinal diseases. Analyzing the composition and metabolomic profile of gut microbiota during acute EBV infection might be instrumental in understanding and controlling EBV.

Methods

Six tree shrews were inoculated with EBV by intravenous injection. Blood was collected at regular intervals thereafter from the femoral vein to detect EBV and inflammatory biomarker. At the same time, tree shrew faeces were collected for 16 S rRNA gene sequencing and Non-targeted metabolomics analysis.

Results

16 S rRNA gene characterization along with β diversity analysis exhibited remarkable alterations in gut microflora structure with a peak at 7 days post-infection(dpi). Some alterations in the relative richness of bacterial taxon were linked to infectious indicators. Of note, Butyricicoccus relative richness was positively linked to EBV presence in the blood and plasma, the opposite correlation was seen with Variovorax and Paramuribaculum. Non-targeted metabolomics indicated the fecal metabolome profile altered during EBV infection, particularly 7 dpi. The relative abundance of geranic acid and undecylenic acid in stool samples was positively linked to systemic inflammatory biomarkers, and an inverse relationship was reported with the estrone glucuronide, linoleic acid, protoporphyrin IX and tyramine.

Conclusion

Collectively, EBV infection in this model correlated with changes in the composition and metabolome profile of the gut microbiota.
Post-growth economics: a must for planetary health justice
Authors: van Woerden Winne Fleur , van de Pas Remco , Curtain Joel
Published: August 2023

Within the global health field, progress is being made to adopt a justice and sustainability-centred approach by advancing what has been named a planetary health agenda. Meanwhile, an increasing number of global health scholars argue for the decolonisation of the field. Yet, amongst these collective efforts to ‘transform’ global health thinking, a thorough analysis of political economy dimensions is often missing. ‘Growthism’, the belief that more production is necessarily good, continues to prevail. Truly committing to a decolonial eco-just global health agenda requires addressing the continuation of colonial arrangements within the structure of the global economy, removing growth dependencies and ushering in post-growth policies.
Using medical storytelling to communicate problems and solutions in the low back pain conundrum: an evidence-based tale of twins
Authors: Murphy Donald R. , Justice Brian D. , Borkan Jeffrey
Published: August 2023

Objectives

Low back pain (LBP) is the number one cause of disability world-wide. It is also the most expensive area in healthcare. Patient-centered innovations are needed. This paper uses medical storytelling to illustrate the common problems that often lead to unnecessary suffering for patients, and costs to society. We present innovative solutions, including narrative interventions.

Methods

We use medical storytelling to present a scenario in which hypothetical twin patients with identical LBP episodes enter the healthcare system, with one twin managed in an appropriate manner, and the other inappropriately.

Results

One twin becomes a chronic LBP sufferer, while the other experiences quick resolution, despite identical conditions. Recommendations are made to de-implement inappropriate action and to implement a more productive approach.

Conclusions

Many patients with LBP descend into chronic pain. This is rarely inevitable based on clinical factors. Much of chronic LBP results from how the condition is handled within the healthcare system. Medical narrative may be one innovation to illustrate the problem of current LBP management, recommend solutions and foster changes in clinical behavior.

Practical implications

The starkly different outcomes for each identical twin are illustrated. Recommendations are made for reframing the situation to de-implement the inappropriate and to implement a more appropriate approach.
Does intraoperative fluoroscopy improve acetabular component positioning and limb-length discrepancy during direct anterior total hip arthroplasty? A meta-analysis
Authors: Sun Changjiao , Lee Woo Guan , Ma Qi , Zhang Xiaofei , Zhao Zhe , Cai Xu
Published: August 2023

Background

The positioning of implant components for total hip arthroplasty (THA) is essential for joint stability, polyethylene liner wear, and range of motion. One potential benefit of the direct anterior approach (DAA) for THA is the ability to use intraoperative fluoroscopy for acetabular cup positioning and limb-length evaluation. Previous studies comparing intraoperative fluoroscopy with no fluoroscopy during DAA have reported conflicting results. This meta-analysis aimed to evaluate whether intraoperative fluoroscopy improves component positioning compared to no fluoroscopy during direct anterior total hip arthroplasty.

Methods

A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted. We searched Web of Science, EMBASE, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, CNKI, VIP, and Wanfang database in May 2023 to identify studies involving intraoperative fluoroscopy versus no fluoroscopy during direct anterior total hip arthroplasty. Finally, we identified 1262 hips assessed in seven studies.

Results

There were no significant differences in terms of acetabular cup inclination angle (ACIA, P = 0.21), ACIA within safe zone rate (P = 0.97), acetabular cup anteversion angle (ACAA, P = 0.26); ACAA within safe zone rate (P = 0.07), combined safe zone rate (P = 0.33), and limb-length discrepancy (LLD, P = 0.21) between two groups.

Conclusion

Even though intraoperative fluoroscopy was not related to an improvement in cup location or LDD. With fewer experienced surgeons, the benefit of intraoperative fluoroscopy might become more evident. More adequately powered and well-designed long-term follow-up studies were required to determine whether the application of the intraoperative fluoroscopy for direct anterior total hip arthroplasty will have clinical benefits and improve the survival of prostheses.
Association of LINC-PINT polymorphisms with lumbar disc herniation risk among Chinese Han population: a case control study
Authors: Wu Yimin , Bai Ming , Yu Yingnan , Wang Yupeng , Zhang Yuan
Published: August 2023

Background

Lumbar disc herniation (LDH) is a complex spinal disease, with multiple genetic polymorphisms being related to its risk. Nevertheless, the role of LINC-PINT polymorphisms in LDH risk has remained unknown. Therefore, this study aimed to investigate the association between LINC-PINT polymorphisms and LDH risk.

Methods

DNA was extracted from 504 LDH patients and 500 healthy controls. Three single nucleotide polymorphisms (SNPs) in LINC-PINT were selected and genotyped using Agena MassARRAY. We used logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) under multiple genetic models to evaluate the association between LINC-PINT polymorphisms and LDH risk. Haploview 4.2 and SNPStats software were used to evaluate the linkage strength of SNPs and the correlation between haplotypes and LDH risk. The impact of SNP-SNP interactions on LDH risk was analyzed using multi-factor dimensionality reduction (MDR).

Results

Results showed that rs157916 (G vs. A: OR = 1.23, FDR-p = 0.029) and rs7801029 (G vs. C: OR = 1.39, FDR-p = 0.006; GG vs. CC: OR = 2.34, FDR-p = 0.038; recessive: OR = 2.13, FDR-p = 0.045; additive: OR = 1.39, FDR-p = 0.030) were associated with an increased risk of LDH. Furthermore, LINC-PINT rs157916 and rs780129 were found to be significantly associated with LDH risk in males. The “GGG” haplotype was associated with increased LDH risk (OR = 1.41, FDR-p = 0.006). MDR analysis indicated that the interaction between rs7801029 and rs16873842 was associated with an increased risk of LDH (OR = 1.47, p = 0.004). Additionally, there were significant differences in C-reactive protein levels among different genotypes of rs157916 and rs780129 (p < 0.05).

Conclusion

This study suggests that LINC-PINT gene polymorphisms (rs157916 and rs7801029) are considered risk factors for LDH in the Chinese Han population and provide a scientific basis for early screening, prevention, and diagnosis of LDH.
New immunotherapy strategies for patients with sarcomas: highlights from the 2023 ASCO annual meeting
Authors: Roulleaux-Dugage Matthieu , Italiano Antoine
Published: August 2023

Immunotherapy has revolutionized cancer treatment, but currently, immuno-oncology agents have not been approved for patients with soft tissue sarcomas. However, there is growing evidence suggesting that immunotherapy could be an effective therapeutic strategy for this group of diseases. Here, we reviewed the latest advances of immunotherapy trials from the 2023 American Society of Clinical Oncology Annual Meeting, including some novel and encouraging combination regimens. Further research is still needed to fully understand the optimal use of these agents in sarcoma treatment.
Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels
Authors: Liepinsh Edgars , Svalbe Baiba , Stelfa Gundega , Grinberga Solveiga , Zvejniece Liga , Schiöth Helgi B. , Dambrova Maija
Published: August 2023

Deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene was identified in probands with autism spectrum disorder (ASD). TMLHE encodes the first enzyme in carnitine biosynthesis, N6-trimethyllysine dioxygenase (TMLD). Researchers have suggested that carnitine depletion could be important for the development of ASD and cognitive, locomotor and social dysfunctions, but previous findings have been inconclusive regarding the specific role of endogenous carnitine. We developed a mouse knockout model with constitutive TMLD enzyme inactivation that exhibited a significant decrease in the carnitine by more than 90% compared to wild-type (WT) mice. However, we did not observe any significant social, cognitive, or repetitive-behavior changes associated with ASD in the knockout mice; muscle strength and coordination were also not affected. In addition, the life expectancy of knockout mice was similar to that of WT mice. In conclusion, knockout of Tmlh in mice does not induce an ASD phenotype or motor dysfunction despite extremely low carnitine and gamma-butyrobetaine concentrations. Moreover, inactivation of TMLD does not induce a phenotype similar to previously described primary carnitine deficiency; indeed, our results showed that low levels of carnitine sustained adequate energy production, muscle function and social behavior in mice.
Loss of microRNA-30a and sex-specific effects on the neonatal hyperoxic lung injury
Authors: Grimm Sandra L. , Reddick Samuel , Dong Xiaoyu , Leek Connor , Wang Amy Xiao , Gutierrez Manuel Cantu , Hartig Sean M. , Moorthy Bhagavatula , Coarfa Cristian , Lingappan Krithika
Published: August 2023

Background

Bronchopulmonary dysplasia (BPD) is characterized by an arrest in lung development and is a leading cause of morbidity in premature neonates. It has been well documented that BPD disproportionally affects males compared to females, but the molecular mechanisms behind this sex-dependent bias remain unclear. Female mice show greater preservation of alveolarization and angiogenesis when exposed to hyperoxia, accompanied by increased miR-30a expression. In this investigation, we tested the hypothesis that loss of miR-30a would result in male and female mice experiencing similar impairments in alveolarization and angiogenesis under hyperoxic conditions.

Methods

Wild-type and miR-30a−/− neonatal mice were exposed to hyperoxia [95% FiO2, postnatal day [PND1-5] or room air before being euthanized on PND21. Alveolarization, pulmonary microvascular development, differences in lung transcriptome, and miR-30a expression were assessed in lungs from WT and miR-30a−/− mice of either sex. Blood transcriptomic signatures from preterm newborns (with and without BPD) were correlated with WT and miR-30a−/− male and female lung transcriptome data.

Results

Significantly, the sex-specific differences observed in WT mice were abrogated in the miR-30a−/− mice upon exposure to hyperoxia. The loss of miR-30a expression eliminated the protective effect in females, suggesting that miR-30a plays an essential role in regulating alveolarization and angiogenesis. Transcriptome analysis by whole lung RNA-Seq revealed a significant response in the miR-30a−/− female hyperoxia-exposed lung, with enrichment of pathways related to cell cycle and neuroactive ligand–receptor interaction. Gene expression signature in the miR-30a−/− female lung associated with human BPD blood transcriptomes. Finally, we showed the spatial localization of miR-30a transcripts in the bronchiolar epithelium.

Conclusions

miR-30a could be one of the biological factors mediating the resilience of the female preterm lung to neonatal hyperoxic lung injury. A better understanding of the effects of miR-30a on pulmonary angiogenesis and alveolarization may lead to novel therapeutics for treating BPD.
KITENIN promotes aerobic glycolysis through PKM2 induction by upregulating the c-Myc/hnRNPs axis in colorectal cancer
Authors: Varlı Mücahit , Kim Sung Jin , Noh Myung-Giun , Kim Yoon Gyoon , Ha Hyung-Ho , Kim Kyung Keun , Kim Hangun
Published: August 2023

Purpose

The oncoprotein KAI1 C-terminal interacting tetraspanin (KITENIN; vang-like 1) promotes cell metastasis, invasion, and angiogenesis, resulting in shorter survival times in cancer patients. Here, we aimed to determine the effects of KITENIN on the energy metabolism of human colorectal cancer cells.

Experimental design

The effects of KITENIN on energy metabolism were evaluated using in vitro assays. The GEPIA web tool was used to extrapolate the clinical relevance of KITENIN in cancer cell metabolism. The bioavailability and effect of the disintegrator of KITENIN complex compounds were evaluated by LC–MS, in vivo animal assay.

Results

KITENIN markedly upregulated the glycolytic proton efflux rate and aerobic glycolysis by increasing the expression of GLUT1, HK2, PKM2, and LDHA. β-catenin, CD44, CyclinD1 and HIF-1A, including c-Myc, were upregulated by KITENIN expression. In addition, KITENIN promoted nuclear PKM2 and PKM2-induced transactivation, which in turn, increased the expression of downstream mediators. This was found to be mediated through an effect of c-Myc on the transcription of hnRNP isoforms and a switch to the M2 isoform of pyruvate kinase, which increased aerobic glycolysis. The disintegration of KITENIN complex by silencing the KITENIN or MYO1D downregulated aerobic glycolysis. The disintegrator of KITENIN complex compound DKC1125 and its optimized form, DKC-C14S, exhibited the inhibition activity of KITENIN-mediated aerobic glycolysis in vitro and in vivo.

Conclusions

The oncoprotein KITENIN induces PKM2-mediated aerobic glycolysis by upregulating the c-Myc/hnRNPs axis.
Rhox6 regulates the expression of distinct target genes to mediate mouse PGCLC formation and ESC self-renewal
Authors: Li Xiaofeng , Chen Peng , Ji Junxiang , Duan Quanchao , Cao Jianjian , Huang Ru , Ye Shou-Dong
Published: August 2023

Background

Mouse embryonic stem cells (mESCs) not only retain the property of self-renewal but also have the ability to develop into primordial germ cell-like cells (PGCLCs). However, knowledge about the mechanisms of transcriptional regulation is still limited. Rhox6, a member of the homeobox family that is located on the X chromosome, is highly expressed within PGCLCs in vivo and in vitro. However, the detailed effects of Rhox6 on PGCLC specification and mESC maintenance remain unclear.

Results

In this study, we found that overexpression of Rhox6 favors the formation of PGCLCs, while depletion of Rhox6 inhibits the generation of PGCLCs. Mechanistically, Rhox6 directly induces the expression of Nanos3 during the specification of PGCLCs. Subsequently, downregulation of Nanos3 expression is sufficient to decrease the ability of Rhox6 to induce PGCLC formation. Moreover, we found that depletion of Rhox6 expression facilitates the self-renewal of mESCs. High-throughput sequencing revealed that suppression of Rhox6 transcription significantly increases the expression of pluripotency genes. Functional studies further demonstrated that Rhox6 directly represses the transcription of Tbx3. Therefore, knockdown of the expression of the latter impairs the self-renewal of mESCs promoted by Rhox6 downregulation.

Conclusions

Our study reveals that overexpression of Rhox6 is beneficial for PGCLC generation through induction of Nanos3, while downregulation of Rhox6 contributes to mESC self-renewal by increasing Tbx3. These findings help elucidate the early development of mouse embryos.
Overview of the current use of levosimendan in France: a prospective observational cohort study
Authors: Cholley Bernard , Bojan Mirela , Guillon Benoit , Besnier Emmanuel , Mattei Mathieu , Levy Bruno , Ouattara Alexandre , Tafer Nadir , Delmas Clément , Tonon David , Rozec Bertrand , Fellahi Jean-Luc , Lim Pascal , Labaste François , Roubille François , Caruba Thibaut , Mauriat Philippe ,   for the ARCOTHOVA study group, Barbot Olivier , Laurent Berthomieu , Besselat Anne-Marie , Katrien Blanchart , Bougle Adrien , Bourgoin Pierre , Arnaud Causeret , Charbonneau Hélène , Cristinar Mircea , Desebbe Olivier , Eljezi Veldat , Genet Thibaud , Grenier Maxime , Guinot Pierre Grégoire , Lebel Stéphane , Levy Yael , Lion François , Mansourati Jacques , Marlière Stéphanie , Martin Anne-Céline , Mebazaa Alexandre , Mohammad Usman , Monsegu Jacques , Nessler Nicolas , Orsel Isabelle , Puymirat Etienne , Recher Morgan , Soussi Sabri , Troussard Vincent , Uhry Sabrina , Zirphile Xavier
Published: August 2023

Background

Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale.

Method

The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year.

Results

The patients included (n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock (n = 250, 41.5%), decompensated heart failure (n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment (n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation (n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up.

Conclusions

We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied.
Outpatient compared to inpatient thyroidectomy on 30-day postoperative outcomes: a national propensity matched analysis
Authors: Traill Lauren , Kendall Mark C. , Caramez Maria Paula , Apruzzese Patricia , De Oliveira Gildasio
Published: August 2023

Background

To address the postoperative outcomes between outpatient and inpatient neck surgery involving thyroidectomy procedures.

Methods

A cohort analysis of surgical patients undergoing primary, elective, total thyroidectomy from multiple United States medical institutions who were registered with the American College of Surgeons National Surgical Quality Improvement Program from 2015 to 2018. The primary outcome was a composite score that included any 30-day postoperative adverse event.

Results

A total of 55,381 patients who underwent a total thyroidectomy were identified comprising of 14,055 inpatient and 41,326 outpatient procedures. A cohort of 13,496 patients who underwent outpatient surgery were propensity matched for covariates with corresponding number of patients who underwent inpatient thyroidectomies. In the propensity matched cohort, the occurrence of any 30-day after surgery complications were greater in the inpatient group, 424 out of 13,496 (3.1%) compared to the outpatient group, 150 out of 13,496 (1.1%), P < 0.001. Moreover, death rates were greater in the inpatient group, 22 out 13,496 (0.16%) compared to the outpatient group, 2 out of 13,496 (0.01%), P < 0.001. Similarly, hospital readmissions occurred with greater frequency in the inpatient group, 438 out of 13,496 (3.2%) compared to the outpatient group, 310 out of 13,496 (2.3%), P < 0.001.

Conclusion

Thyroidectomy procedures performed in the outpatient setting had less rates of adverse events, including serious postoperative complications (e.g., surgical site infection, pneumonia, progressive renal insufficiency). In addition, patients who had thyroidectomy in the outpatient setting had less 30-day readmissions and mortality. Surgeons should recognize the benefits of outpatient thyroidectomy when selecting disposition of patients undergoing neck surgery.
Identification of robust and generalizable biomarkers for microbiome-based stratification in lifestyle interventions
Authors: Chen Jiarui , Siliceo Sara Leal , Ni Yueqiong , Nielsen Henrik B. , Xu Aimin , Panagiotou Gianni
Published: August 2023

Background

A growing body of evidence suggests that the gut microbiota is strongly linked to general human health. Microbiome-directed interventions, such as diet and exercise, are acknowledged as a viable and achievable strategy for preventing disorders and improving human health. However, due to the significant inter-individual diversity of the gut microbiota between subjects, lifestyle recommendations are expected to have distinct and highly variable impacts to the microbiome structure.

Results

Here, through a large-scale meta-analysis including 1448 shotgun metagenomics samples obtained longitudinally from 396 individuals during lifestyle studies, we revealed Bacteroides stercoris, Prevotella copri, and Bacteroides vulgatus as biomarkers of microbiota’s resistance to structural changes, and aromatic and non-aromatic amino acid biosynthesis as important regulator of microbiome dynamics. We established criteria for distinguishing between significant compositional changes from normal microbiota fluctuation and classified individuals based on their level of response. We further developed a machine learning model for predicting “responders” and “non-responders” independently of the type of intervention with an area under the curve of up to 0.86 in external validation cohorts of different ethnicities.

Conclusions

We propose here that microbiome-based stratification is possible for identifying individuals with highly plastic or highly resistant microbial structures. Identifying subjects that will not respond to generalized lifestyle therapeutic interventions targeting the restructuring of gut microbiota is important to ensure that primary end-points of clinical studies are reached.
Study protocol for a multi-level cross-sectional study on the equitable reach and implementation of coordinated specialty care for early psychosis
Authors: Oluwoye Oladunni , Lissau Ari , Stokes Sheldon , Selloni Alexandria T. , James Najé , Amiri Solmaz , McDonell Michael G. , Anglin Deidre M.
Published: August 2023

Background

Approximately 115,000 young adults will experience their first episode of psychosis (FEP) each year in the USA. Coordinated specialty care (CSC) for early psychosis is an evidence-based early intervention model that has demonstrated effectiveness by improving quality of life and reducing psychiatric symptoms for many individuals. Over the last decade, there has significant increase in the implementation of CSC programs throughout the USA. However, prior research has revealed difficulties among individuals and their family members accessing CSC. Research has also shown that CSC programs often report the limited reach of their program to underserved populations and communities (e.g., ethnoracial minorities, rural and low socioeconomic neighborhoods). Dissemination and implementation research focused on the equitable reach and implementation of CSC is needed to address disparities at the individual level.

Methods

The proposed study will create a novel integrative multi-level geospatial database of CSC programs implemented throughout the USA that will include program-level data (e.g., geocoded location, capacity, setting, role availability), provider-level data (race, ethnicity, professional credentials), and neighborhood-level census data (e.g., residential segregation, ethnic density, area deprivation, rural-urban continua, public transit time). This database will be used to characterize variations in CSC programs by geographical location and examine the overall reach CSC programs to specific communities. The quantitative data will be combined with qualitative data from state administrators, providers, and service users that will inform the development of dissemination tools, such as an interactive dashboard, that can aid decision making.

Discussion

Findings from this study will highlight the impact of outer contextual determinants on implementation and reach of mental health services, and will serve to inform the future implementation of CSC programs with a primary focus on equity.