bluuebunny/crossref_metadata_2025 huggingface dataset:
The managers' perspectives on service providing in women's harm reduction centers during the COVID-19 pandemic: mixed method study
Authors: Rahmani Azam , Janatolmakan Maryam , Rezaei Elham , Tabarrai Malihe
Published: July 2024

Background

The COVID-19 pandemic posed significant challenges for managers overseeing women's harm reduction centers. This study seeks to capture managers' perspectives on the service providing in women's harm reduction centers during the COVID-19 pandemic.

Methods

This convergent mixed-method study conducted in three provinces of Iran: Tehran, Khuzestan, and Kermanshah. The study was carried out between January and May 2023. In the quantitative part, the researchers utilized reports from 10 center managers. A researcher-designed questionnaire was employed to collect data on a wide range of services and referrals provided by the centers. The qualitative part of the research involved conventional content analysis and included 12 individual interviews. Two directors from the Ministry of Health and ten managers of women’s harm reduction centers participated in the interviews. During the interpretation phase, the researchers compared the quantitative and qualitative findings to obtain a comprehensive understanding of the topic.

Results

During the quantitative stage of the study, it was observed that all the managers were women, with an average age of 40.7 ± 7 years. More than half of the managers had obtained a postgraduate education (n = 6, 60%), and a majority of them were married (n = 7, 70%). Additionally, 40% of the managers (n = 4) were working as contractors. During the non-COVID-19 period, there were higher coverage by centers and residents, more referrals of non-injecting drug users and sex workers, and a higher number of group counseling sessions in all three provinces compared to the COVID-19 period. The qualitative analysis revealed two primary themes: "challenges" and "capabilities."

Conclusions

During the COVID-19 pandemic, providing some services and client referrals decreased in the centers, and center managers faced increased challenges. Many of these challenges were in the communication, executive, management, structure, education, financial, civilization, facilities, and socio-cultural sectors. Managers used their skills to manage and control these challenges. It is important to focus on these challenges and managerial capabilities to effectively handle future crises.
Ikaros sets the threshold for negative B-cell selection by regulation of the signaling strength of the AKT pathway
Authors: Ehm Patrick A. H. , Horn Stefan , Hoffer Konstantin , Kriegs Malte , Horn Michael , Giehler Susanne , Nalaskowski Marcus , Rehbach Christoph , Horstmann Martin A. , Jücker Manfred
Published: July 2024

Inhibitory phosphatases, such as the inositol-5-phosphatase SHIP1 could potentially contribute to B-cell acute lymphoblastic leukemia (B-ALL) by raising the threshold for activation of the autoimmunity checkpoint, allowing malignant cells with strong oncogenic B-cell receptor signaling to escape negative selection. Here, we show that SHIP1 is differentially expressed across B-ALL subtypes and that high versus low SHIP1 expression is associated with specific B-ALL subgroups. In particular, we found high SHIP1 expression in both, Philadelphia chromosome (Ph)-positive and ETV6-RUNX1-rearranged B-ALL cells. As demonstrated by targeted knockdown of SHIP1 by RNA interference, proliferation of B-ALL cells in vitro and their tumorigenic spread in vivo depended in part on SHIP1 expression. We investigated the regulation of SHIP1, as an important antagonist of the AKT signaling pathway, by the B-cell-specific transcription factor Ikaros. Targeted restoration of Ikaros and pharmacological inhibition of the antagonistic casein kinase 2, led to a strong reduction in SHIP1 expression and at the same time to a significant inhibition of AKT activation and cell growth. Importantly, the tumor suppressive function of Ikaros was enhanced by a SHIP1-dependent additive effect. Furthermore, our study shows that all three AKT isoforms contribute to the pro-mitogenic and anti-apoptotic signaling in B-ALL cells. Conversely, hyperactivation of a single AKT isoform is sufficient to induce negative selection by increased oxidative stress. In summary, our study demonstrates the regulatory function of Ikaros on SHIP1 expression in B-ALL and highlights the relevance of sustained SHIP1 expression to prevent cells with hyperactivated PI3K/AKT/mTOR signaling from undergoing negative selection.
Childbirth preparation and its facilitating and inhibiting factors from the perspectives of pregnant and postpartum women in Tabriz-Iran: a qualitative study
Authors: Alizadeh-Dibazari Zohreh , Abbasalizadeh Fatemeh , Mohammad-Alizadeh-Charandabi Sakineh , Jahanfar Shayesteh , Mirghafourvand Mojgan
Published: July 2024

Background

The World Health Organization recognizes childbirth preparation as an essential component of antenatal care, as it plays a crucial role in reducing maternal mortality and improving women's childbirth experience. Countries worldwide have implemented various interventions to assist women in preparing for childbirth, based on their own resources. This study was conducted with the aim of exploring the perspectives of pregnant and postpartum women on childbirth preparation and the facilitating and inhibiting factors, in Tabriz, Iran.

Methods

This qualitative study was conducted with 25 participants, selected purposively among pregnant women in weeks 37 to 40 of gestation and postpartum women within 10 days to 6 weeks after childbirth. Data collection was done through semi-structured, in-depth individual interviews using an interview guide. The data was analyzed using content analysis method with conventional approach.

Results

The perspectives of pregnant and postpartum women regarding childbirth preparation revealed that factors such as maternal health during pregnancy, having an antenatal care plan, improving health literacy, and developing a birth plan were identified as crucial elements for effective childbirth preparation. Additionally, mental and emotional preparation, support, financial planning, participation in preparation classes, and awareness of childbirth methods were recognized as facilitators. On the other hand, insufficient mental and emotional preparedness, inadequate support, weak antenatal care, information deficiencies, insufficient physical activity, and a lack of a birth plan were identified as barriers.

Conclusion

The findings highlight the multifaceted nature of childbirth preparedness, necessitating the involvement of families, the healthcare system, and the entire community. Utilizing the study results in strategic planning for pre-pregnancy, during pregnancy, and inter-pregnancy care can enhance childbirth preparedness and contribute to achieving Iran's population rejuvenation policy goals.
Dual-task improvement of older adults after treadmill walking combined with blood flow restriction of low occlusion pressure: the effect on the heart–brain axis
Authors: Chen Yi-Ching , Lo I-Ping , Tsai Yi-Ying , Zhao Chen-Guang , Hwang Ing-Shiou
Published: July 2024

Objective

This study explored the impact of one session of low-pressure leg blood flow restriction (BFR) during treadmill walking on dual-task performance in older adults using the neurovisceral integration model framework.

Methods

Twenty-seven older adults participated in 20-min treadmill sessions, either with BFR (100 mmHg cuff pressure on both thighs) or without it (NBFR). Dual-task performance, measured through light-pod tapping while standing on foam, and heart rate variability during treadmill walking were compared.

Results

Following BFR treadmill walking, the reaction time (p = 0.002) and sway area (p = 0.012) of the posture dual-task were significantly reduced. Participants exhibited a lower mean heart rate (p < 0.001) and higher heart rate variability (p = 0.038) during BFR treadmill walking. Notably, BFR also led to band-specific reductions in regional brain activities (theta, alpha, and beta bands, p < 0.05). The topology of the EEG network in the theta and alpha bands became more star-like in the post-test after BFR treadmill walking (p < 0.005).

Conclusion

BFR treadmill walking improves dual-task performance in older adults via vagally-mediated network integration with superior neural economy. This approach has the potential to prevent age-related falls by promoting cognitive reserves.
The associations between the Geriatric Nutritional Risk Index and all-cause, cancer-specific, and cardiovascular mortality in the U.S. population: a large-scale pooled survey
Authors: Han Kun , Wang Tianhong , Zou Congcong , Li Tao , Zhou Leng
Published: July 2024

Background

Previous studies have reported a close association between the Geriatric Nutritional Risk Index (GNRI) and various conditions. However, the association between the GNRI and mortality remains unclear. To examine the correlation between the GNRI and all-cause, cancer-specific, and cardiovascular mortality, this study was performed.

Methods

We analyzed elderly participants in the National Health and Nutrition Examination Survey from 2005 to 2016. The GNRI was calculated using body mass index and serum albumin. Kaplan-Meier survival curves were drawn to compare the survival probability between the normal and decreased GNRI groups. Weighted multivariate Cox regression and restricted cubic spline (RCS) models were employed to determine the linear and non-linear associations of the GNRI with all-cause, cancer-specific, and cardiovascular mortality.

Results

A total of 3,276 participants were included in the analysis. The Kaplan-Meier survival curve showed that the decreased GNRI group had a lower survival probability for all-cause mortality and cancer-specific mortality (P < 0.001) but not for cardiovascular mortality (P > 0.05). In the full regression models, the decreased group had a higher risk of all-cause mortality (HR = 1.67, 95% CI = 1.21–2.30, P = 0.002), and cancer-specific mortality (HR = 2.20, 95% CI = 1.32–3.67, P = 0.003) than the normal group. For cardiovascular mortality, no significant association with GNRI (HR = 1.39, 95% CI = 0.60–3.22, P = 0.436) was detected. Notably, the RCS analysis identified a linear downward trend between the GNRI and all-cause, alongside cancer-specific mortalities (all P for overall < 0.05). The time-dependent Receiver Operating Characteristic (ROC) analysis unveiled the predictive power of the GNRI for 5-year all-cause mortality, cancer mortality, and cardiovascular mortality was 0.754, 0.757, and 0.836, respectively, after adjusting for covariates.

Conclusions

Individuals with a decreased GNRI had increased risks of all-cause, and cancer-specific mortality. There were linear associations of the GNRI with all-cause, and cancer-specific mortality. Nutritional status should be carefully monitored, which may improve the overall prognosis for the general population.
Efficacy comparison between intramedullary nail fixation and plate fixation in distal tibia fractures: a meta-analysis of randomized controlled trials
Authors: Li Xiaobin , Chen Kaipeng , Xue Haipeng , Cheng Junwen , Yu Xiaoping
Published: July 2024

Background

Intramedullary nail (IMN) and plate fixation are the most commonly used surgical modalities for distal tibia fractures. However, the superiority of their efficacy regarding functional outcomes and complications remains controversial. Here, we performed a systematic review and meta-analysis to compare the efficacy of these two modalities.

Methods

Randomized controlled trials (RCTs) comparing the efficacy of IMN and plate fixation in distal tibia fractures were searched in PubMed, Web of Science, EMBASE, ClinicalTrials.gov, and Cochrane Library up to January 31, 2024. Weighted mean difference (WMD) and odds ratio (OR) with corresponding 95% confidence interval (CI) were estimated using a random-effect model for continuous and categorical outcomes, respectively.

Results

A total of 20 RCTs comprising 1528 patients were included. Compared with plate fixation, IMN significantly shortened surgery time (WMD=-10.73 min, 95%CI: -15.93 to -5.52), union time (WMD=-1.56 weeks, 95%CI: -2.82 to -0.30), and partial (WMD=-1.71 weeks, 95%CI: -1.91 to -0.43) and full (WMD=-2.61 weeks, 95%CI: -3.53 to -1.70) weight-bearing time. IMN was associated with markedly reduced risk of wound infection (OR = 0.44, 95%CI: 0.31–0.63) and secondary procedures (OR = 0.72, 95%CI: 0.55–0.95), but increased the risk of malunion (OR = 1.53, 95%CI: 1.02–2.30) and anterior knee pain (OR = 3.94, 95%CI: 1.68–9.28). The rates of nonunion, delayed union, and functional assessment scores did not significantly differ between the two groups. The percentages of patients obtaining an excellent functional outcome or an excellent and good functional outcome post-operation were comparable.

Conclusions

Both IMN and plate fixation are effective modalities for the surgical treatment of distal tibia fractures. IMN seems to be preferred since it confers more advantages, but the elevated rates of malunion and knee pain require attention. The decision on fixation modality should be tailored to the specific fracture, considering these pros and cons.
The possible short-term of Nigella sativa – L in the management of adolescent polycystic ovarian syndrome: results of a randomized controlled trial
Authors: Mahmoudian Azamsadat , Ashouri Akram , Bilandi Roghaieh Rahmani , Mohammadzadeh Fatemeh , Dashti Sareh , Bahri Narjes
Published: July 2024

Background

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age and the most common cause of infertility due to anovulation. PCOS in adolescents is concerning. Nigella sativa is effective in improving gonadotropins and sex hormones. The current study was designed to investigate the effect of Nigella sativa supplementation on PCOS symptoms and their severity in adolescents.

Methods

The current randomized clinical trial was conducted on 114 adolescents with PCOS who were referred to gynecologist offices and clinics in Gonabad, Iran from March 2022 to March 2023. Participants were randomly allocated to the intervention (Nigella sativa 1000 mg/day) and control (10 mg/day medroxyprogesterone from the 14th day of the cycle for 10 nights) groups. The study duration was 16 weeks. Ovarian volume (measured by ultrasound), anthropometric and blood pressure; serum testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), luteinizing hormone (LH), hirsutism severity (Ferriman–Gallwey score) levels were evaluated before and after the study.

Results

Data from 103 participants (control group = 53, intervention group = 50) were analyzed. The mean age of participants was 17.0 (Interquartile range [IQR]:2.0). The mean difference in hirsutism score changes (p < 0.001), right (p = 0.002), and left (p = 0.010) ovarian volume, serum LH (p < 0.001) and testosterone (p = 0.001) were significantly higher in the intervention group compared to the control group. The frequency of oligomenorrhea, menometrorrhagia, and amenorrhea, were significantly reduced after the study in the intervention group compared to the control group (ps < 0.001).

Conclusions

Short-term Nigella sativa supplementation may be effective in reducing ovarian volume and improving hormonal balance, and menstrual irregularities in adolescents with PCOS. Further research and long-term studies are warranted to validate the potential therapeutic effects of Nigella sativa in adolescents with PCOS.

IRCT registration number

IRCT20221017056209N1 Registration date: 2022-11-22.
Prognostic value of serial (1,3)-β-d-glucan measurements in ICU patients with invasive candidiasis
Authors: Carelli Simone , Posteraro Brunella , Torelli Riccardo , De Carolis Elena , Vallecoccia Maria Sole , Xhemalaj Rikardo , Cutuli Salvatore Lucio , Tanzarella Eloisa Sofia , Dell’Anna Antonio Maria , Lombardi Gianmarco , Cammarota Fabiola , Caroli Alessandro , Grieco Domenico Luca , Sanguinetti Maurizio , Antonelli Massimo , De Pascale Gennaro
Published: July 2024

Background

To determine whether a decrease in serum (1,3)-β-d-glucan (BDG) was associated with reduced mortality and to investigate the performance of BDG downslope in predicting clinical outcome in invasive candidiasis.

Methods

Observational cohort study in ICU patients over a ten-year period (2012–2022) in Italy. Proven invasive candidiasis with at least 2 BDG determinations were considered.

Results

In the study population of 103 patients (age 47 [35–62] years, SAPS II score 67 [52–77]) 68 bloodstream and 35 intrabdominal infections were recorded. Serial measurements showed that in 54 patients BDG decreased over time (BDG downslope group) while in 49 did not (N-BDG downslope group). Candida albicans was the pathogen most frequently isolated (61%) followed by C. parapsilosis (17%) and C. glabrata (12%), in absence of any inter-group difference. Invasive candidiasis related mortality was lower in BDG downslope than in N-BDG downslope group (17% vs 53%, p < 0.01). The multivariate Cox regression analysis showed the association of septic shock at infection occurrence and chronic liver disease with invasive candidiasis mortality (HR [95% CI] 3.24 [1.25–8.44] p = 0.02 and 7.27 [2.33–22.66] p < 0.01, respectively) while a BDG downslope was the only predictor of survival (HR [95% CI] 0.19 [0.09–0.43] p < 0.01). The area under the receiver operator characteristic curve for the performance of BDG downslope as predictor of good clinical outcome was 0.74 (p = 0.02) and our model showed that a BDG downslope > 70% predicted survival with both specificity and positive predictive value of 100%.

Conclusions

A decrease in serum BDG was associated with reduced mortality and a steep downslope predicted survival with high specificity in invasive candidiasis.
Optimization of kidney function in cardiac surgery patients with intra-abdominal hypertension: expert opinion
Authors: Moll Vanessa , Khanna Ashish K. , Kurz Andrea , Huang Jiapeng , Smit Marije , Swaminathan Madhav , Minear Steven , Parr K. Gage , Prabhakar Amit , Zhao Manxu , Malbrain Manu L. N. G.
Published: July 2024

Cardiac surgery-associated acute kidney injury (CSA-AKI) affects up to 42% of cardiac surgery patients. CSA-AKI is multifactorial, with low abdominal perfusion pressure often overlooked. Abdominal perfusion pressure is calculated as mean arterial pressure minus intra-abdominal pressure (IAP). IAH decreases cardiac output and compresses the renal vasculature and renal parenchyma. Recent studies have highlighted the frequent occurrence of IAH in cardiac surgery patients and have linked the role of low perfusion pressure to the occurrence of AKI. This review and expert opinion illustrate current evidence on the pathophysiology, diagnosis, and therapy of IAH and ACS in the context of AKI.
Emotional intelligence impact on academic achievement and psychological well-being among university students: the mediating role of positive psychological characteristics
Authors: Shengyao Ye , Xuefen Lin , Jenatabadi Hashem Salarzadeh , Samsudin Nadia , Chunchun Ke , Ishak Zahari
Published: July 2024

The main objective of this study is to examine the relationship of emotional intelligence with psychological well-being and academic achievement through positive psychological characteristics among university students in China. The study was conducted with postgraduate and undergraduate students. The integration of emotional intelligence theory and positive psychological theory was used in this study. The introduced framework included emotional intelligence as the main independent variable, self-efficacy, motivation, and resilience as three mediators, and psychological well-being and academic achievement as two dependent variables. A survey was conducted among 518 students, and structural equation modelling was used to analyse the data. The study found that emotional intelligence was positively related to positive psychological characteristics, psychological well-being, and academic achievement, and the effects were stronger among postgraduate students. Also, positive psychological characteristics, which include self-efficacy, motivation, and resilience, mediate the relationship between emotional intelligence and psychological well-being and academic achievement, and the relationship was stronger among postgraduate students. Proper coping strategies and mechanisms can be helpful to improve both psychological well-being and academic achievement at the same time among university students.
The rise of urbanism and exchange network: reconstruction of a 4000-year local history of Xinjiang, northwestern China
Authors: Wang Yongqiang , Chen Yi , Cao Huihui , Liu Ruiliang , Staff Richard A. , Du Linyao , Yuan Xiao , Zhang Shanjia , Ma Jian , Qiu Menghan
Published: July 2024

Urbanization is one of the milestones in the development of human society. Many regions in the southern parts of ‘the old world’ demonstrating an early emergence of agriculture also witnessed the flourishing of some of the earliest cities. Recent, yet still sparse, archaeological evidence appears to indicate a relatively later time for early urbanism in central Eurasia. However, given its vital geographic location and cultural nexus between East and West, more attention should be paid to the sedentary communities and their cities in oases amid the vast droughty desert, particularly in light of the rapidly increasing number of publications on early pastoralism and related communication routes along mountain chains and rivers. This study reveals the trajectory of urbanization and its role in the establishment of an exchange network in Xinjiang’s oasis region via reconstruction of the chronological sequence of the local societal history of the Baiyang River Basin along the southern piedmont of the Eastern Tianshan Mountains. A thorough archaeological investigation and refined radiocarbon dating programme was carried out and coupled with information from historical documentation within a Bayesian statistical framework. The results indicate three pulses of local urbanization during: the Early Iron Age, Tang–Yuan period, and Qing Dynasty, respectively. Combining this with evidence from other parts of Xinjiang, we re-evaluate the role of oasis urbanism in the promotion of trans-regional exchange.
Multidisciplinary treatment of giant thymoma, paving the way to complete surgical resection: a case report
Authors: Makita Ayaka , Nakamura Shota , Setogawa Tomohiro , Imamura Yoshito , Okado Shoji , Nomata Yuji , Watanabe Hiroki , Kawasumi Yuta , Kadomatsu Yuka , Ueno Harushi , Kato Taketo , Mizuno Tetsuya , Chen-Yoshikawa Toyofumi Fengshi
Published: July 2024

Background

A multidisciplinary treatment approach is recommended for patients with extensive, advanced, or recurrent thymomas. However, detailed treatment strategies, such as chemotherapy regimens and optimal surgical procedures, are still under debate.

Case presentation

We report a case of gigantic locally advanced thymoma. A 70-year-old male was referred to our hospital following the detection of abnormal chest shadows. Chest X-ray and computed tomography (CT) scans revealed a 21-cm mass in the anterior mediastinum, encircling the pulmonary hilum and extending into the left thoracic cavity. PET/CT showed increased 18F-fluorodeoxyglucose uptake at the tumor site. Based on a trans-percutaneous CT-guided needle biopsy, the tumor was diagnosed as a Type B2 thymoma at the clinical IIIA stage. The patient underwent four cycles of preoperative induction chemotherapy, including cisplatin, doxorubicin, and methylprednisolone (CAMP), resulting in a partial response; the tumor shrank to 12 cm and FDG uptake decreased. Considering the patient’s age and comorbidities, we performed total thymectomy, along with partial resections of the parietal, mediastinal and visceral pleura, pericardium, and left upper lobectomy. This approach achieved complete histological resection, mitigating the risk of recurrence. Pathological analysis confirmed a thymoma, ypT3 (lung) N0M0 stage IIIA, with no malignancy in the pericardial or pleural effusions. No recurrence was detected 9 months post-surgery.

Conclusions

We report a case of giant thymoma successfully treated with multidisciplinary strategy. Surgical treatment alone may not have achieved complete resection, but after inducing significant tumor shrinkage with preoperative CAMP therapy, we were able to achieve complete resection. This treatment strategy may be effective in large thymoma cases.
Combined neurokinin-1 receptor antagonist and sorafenib is a promising approach for hepatocellular carcinoma therapy
Authors: Sedky Heba E. , Elwany Yasmine N. , Alfy Eman S. El , Elwany Mona N. , Nabil Yasmin M. , Manna Hazem F. , Abdelaziz Mohamed A. , Hadidy Wessam F. El
Published: July 2024

Background

HCC (Hepatocellular carcinoma) is the most common primary malignant cancer in the liver. Treatment options to incurable HCC such as sorafenib, an oral multikinase inhibitor, had numerous side effects and questionable effectiveness. Neurokinin-1 receptor (NK1R) have a major role in inflammation and tumour environment including the resistance to cell death, the induction of angiogenesis and the promotion of cell migration and proliferation. Additionally, NK-1R is over-expressed in human tumour cells including HCC. Moreover, Aprepitant, one of the NK-1R antagonists exerts multiple antitumor activities (antiproliferative, apoptotic, antimigration, and antiangiogenesis) in vivo and in vitro.

Study aim

To analyze the effectiveness of combining sorafenib with aprepitant in the management of HCC (experimental).

Patients and methods

In this retrospective experimental study, the human HCC cell line, HepG2, cells were exposed to increasing concentrations of sorafenib alone, aprepitant alone and combination of both sorafenib and aprepitant evaluation of cytotoxicity, apoptosis, MMP-9, VEGF, NF-kB p-65, p-AKT and p-ERK were done. Moreover, The extent of the NK-1 receptor expression was assessed by immunocytochemistry on 50 HCC paraffin blocks of Egyptian HCC patients and another 50 paraffin blocks of liver cirrhosis only as a control.

Results

Decreased levels of MMP-9, VEGF, NF-kB p-65, p-AKT and p-ERK was more substantial in the combination therapy compared to sorafenib alone and aprepitant alone. Moreover, the rate of apoptosis and cytotoxicity were significantly higher in the combination treatment group than the monotherapy groups with more anti inflammatory, anti angiogentic and anti metastatic effects. Also, among the 50 HCC paraffin blocks, the majority (60%) showed a strong NK-1 expression; which significantly (p < 0.05) correlated with the progression free survival (PFS) but not the overall survival (OS) of the patients when applying multivariate analysis.

Conclusion

HCC had strong expression and immunostaining for NK1R.Therefore, combined aprepitant and sorafenib may be a promising approach in HCC treatment compared to each one alone.
The utility of various predictive equations in patients with severe Obstructive Sleep Apnea: a clinical practice viewpoint in settings with limited resources
Authors: Gharib Ahmed , Elsheikh Mai S. , Galal Iman
Published: July 2024

Background

The continuous positive airway pressure (CPAP) needed for the treatment of obstructive sleep apnea (OSA) can be determined after a manual titration study which is often expensive and time consuming. Hence, different predictive equations were suggested to simplify the treatment of OSA. The purpose of this work was to compare the CPAP identified with manual titration with that calculated using various equations in a cohort of patients with severe OSA.

Methods

This work was conducted on patients diagnosed with severe OSA. Data collected included full medical history, demographic and anthropometric measures, polysomnography results, and the CPAP pressure obtained after manual titration which was further compared to 15 predictive equations retrieved from the literature.

Results

A total of 166 patients [137 (82.5%) males and 29 (17.5%) females] with severe OSA were recruited in the study. Their mean age was 55.91 ± 12.64, and their baseline diagnostic apnea hypopnea index was 71.75 ± 23.70. The mean CPAP manual titration pressure was 11.31 ± 2.9 cmH2O. Non-significant statistical difference was found (p > 0.05) when the mean titration pressure was calculated by Eqs. 2 (11.36 ± 2), 3 (11.55 ± 1.68), 10 (11.51 ± 2.29), 11 (11.14 ± 2.04), and 14 (11.71 ± 2.06), whereas the mean titration pressure calculated by Eqs. 1, 4, 5, 6, 7, 8, 9, 12, 13, and 15 differed significantly from the manual titration pressure (p < 0.05).

Conclusion

Predictive equations suggested to calculate CPAP pressure, albeit simple and easy to apply, yielded variable results and should be investigated carefully before their use into clinical practice.
Magnetic-free chiral eigenmode spectroscopy for simultaneous sensitive measurement of optical rotary dispersion and circular dichroism
Authors: Zhou Wenpeng , Ruan Ya-Ping , Wu Haodong , Zhang Han , Tang Jiang-Shan , Xie Zhenda , Tang Lei , Wang Yu , Ji Yue-E , Jia Kunpeng , Qiu Cheng-Wei , Lu Yan-Qing , Xia Keyu
Published: July 2024

Chirality, defined by Lord Kelvin, refers to the geometric symmetry property of an object that cannot be superposed onto its mirror image using rotations and translations. The material’s chirality can be probed with light as the optical activity: optical rotary dispersion (ORD) and circular dichroism (CD). It is still challenging to yield extremely sensitive ORD and CD for very weak chirality and measure both simultaneously. Cavity ringdown polarimetry has been reported to improve ORD detection sensitivity with the absence of equally important CD signature, at the price of high cavity finesse near 400, frequency-locking sophistication, and large magnetic field. Here, we report a unique recipe to demonstrate the simultaneous measurement of ORD and the CD by separately observing the chiral eigenmode spectra from a bowtie optical cavity with a finesse about 30, without resorting to frequency locking or magnetic field. We obtain a sensitivity of $$\sim 2.7\times 10^{-3} \text {deg}/\sqrt{\text {Hz}}$$

∼
2.7
×

10

-
3

deg
/

Hz

for ORD, $$\sim 8.1 \times 10^{-6} /\sqrt{\text {Hz}}$$

∼
8.1
×

10

-
6

/

Hz

for CD, and a spectral resolution of $$0.04~\text {pm}$$

0.04

pm

within a millisecond-scale measurement. We present a cost-effective yet ultrasensitive account for chiral chromatography, the conformational dynamics and chiroptical analysis of biological samples which particularly exhibit weak and narrow spectral signals.
A Longitudinal Study of Glucose Tolerance in Cystic Fibrosis: The Central Role of Beta Cell Functional Mass
Authors: Piona Claudia , Mozzillo Enza , Tosco Antonella , Zusi Chiara , Emiliani Federica , Volpi Sonia , Di Candia Francesca , Raia Valeria , Boselli Maria Linda , Trombetta Maddalena , Cipolli Marco , Bonadonna Riccardo C , Maffeis Claudio
Published: July 2024

Context

The pathophysiological mechanisms underlying the natural history of glucose intolerance and its fluctuations in subjects with cystic fibrosis (CF) are still unclear.

Objective

To investigate the relationship between longitudinal changes in glucose tolerance and concomitant changes in the main parameters of insulin secretion/metabolism/action determining glucose regulation in subjects with CF.

Methods

Insulin sensitivity and glucose-stimulated insulin secretion (GSIS, a biomarker of beta cell functional mass), as estimated by the Oral Glucose Sensitivity Index (OGIS) and by a sophisticated mathematical model, respectively, and insulin clearance were assessed in 127 subjects with CF, aged 10-25 years, who underwent 2 oral glucose tolerance tests over an at least 1-year follow-up period. Subjects were classified a posteriori as regressors (improved glucose tolerance), stable, or progressors (worsened glucose tolerance). The interplay between beta cell compensatory action and insulin sensitivity over time was analyzed by vector plots of insulin clearance adjusted GSIS (PCadj) vs OGIS.

Results

OGIS decreased in progressors and stable. Insulin clearance decreased in both regressors and progressors. GSIS (beta cell functional mass) improved in regressors and worsened in progressors, whereas it did not change in stable. Vector plot analysis confirmed that glucose regulation changed differently in each group. Multinomial logistic regression analysis showed that baseline glucose tolerance and GSIS changes were the only significant predictors of the changes in glucose tolerance (P < .02, R2 Nagelkerke = 0.55), whereas age, gender, z body mass index, CF genotypes, and baseline adjusted proportional control were not.

Conclusion

In subjects with CF, changes in beta cell functional mass are associated with favorable or detrimental changes of glucose tolerance over time.
Primary Cilia are Required for Cell-Type Determination and Angiogenesis in Pituitary Development
Authors: Yoshida Saishu , Tsuneoka Yousuke , Tsukada Takehiro , Nakakura Takashi , Kawamura Akira , Kai Wataru , Yoshida Kiyotsugu
Published: July 2024

The functional maturation of the pituitary gland requires adequate cell differentiation and vascular network formation. Although spatiotemporal signaling and transcription factors are known to govern pituitary development, the involvement of primary cilia, nonmoving hair-like organelles, remains unclear. In this study, we uncovered the contribution of primary cilia to cell-type determination and vascular network formation during pituitary development. Homozygous knockout mice lacking a ciliary kinase, Dyrk2−/−, exhibit abnormalities in ciliary structure and pituitary hypoplasia, accompanied by varying degrees of failure in differentiation among all types of hormone-producing cells in the anterior lobe. Aberrations in cell differentiation in Dyrk2−/− mice arise from a decrease in the expression of crucial transcription factors, Lhx4, Lhx3, and Prop1, resulting from the inactivity of Hedgehog (Hh) signaling during the early stages of development. Furthermore, the loss of Dyrk2 results in vascular system abnormalities during the middle to late stages of development. Mechanistically, transcriptome analyses revealed the downregulation of vitronectin-integrin αvβ3-VEGFR2 signaling, essential for orchestrating vascular development. Collectively, our findings demonstrate that primary cilia play a pivotal role as critical regulators of cell survival, cell determination, and angiogenesis during pituitary gland development through the activation of Hh signaling. These findings expand our understanding of the potential link between pituitary dysfunction in human disorders and ciliopathies.
Effect and Safety of Apatinib as Neoadjuvant Therapy in Locally Advanced Differentiated Thyroid Cancer: A Phase 2 Trial
Authors: Qian Kai , Wang Yunjun , An Ning , Liu Chunhao , Guo Kai , Yang Lingyi , Wang Jun , Li Xiaoyi , Wang Zhuoying
Published: July 2024

Context

Presently, there is a paucity of prospective clinical trials investigating neoadjuvant therapy for locally advanced thyroid cancer.

Objective

This study was a multicenter, open-label, single-arm, phase II trial evaluating the efficacy and safety of apatinib as neoadjuvant therapy in patients with local advanced differentiated thyroid cancer (DTC).

Methods

Patients were treated with preoperative apatinib over a course of 2 to 4 cycles, culminating in surgical resection. The primary endpoints were objective response rate (ORR) and disease control rate (DCR); the secondary endpoints were the rate of R0 surgery, alterations in serum thyroglobulin levels, disease-free survival, and adverse events (AEs).

Results

A total of 14 patients who met the inclusion criteria were administered neoadjuvant apatinib. Among these, 13 patients underwent surgical procedures following apatinib treatment and were enrolled in the ITT population. The ORR was 53.8% and the DCR was 100%. Of the patients, 84.6% received R0 surgery, while the remaining 15.4% underwent R1 resection. Predominant among the observed AEs were hypertension, hand–foot syndrome, hepatic dysfunction, proteinuria, and hypothyroidism, with no instances of grade 4 or 5 AEs reported. Subsequent to surgery, patients were followed up for a median period of 34 months, during which disease progression occurred in 5 individuals (35.7%), encompassing 3 cases of locoregional recurrences and 2 cases of distant metastases.

Conclusion

Apatinib may be an effective agent in the use of neoadjuvant therapy for locally advanced DTC. Patients may therefore benefit from surgical outcomes and their long-term prognosis.
Navigating the Intersection Between the Orbit and the Skull Base: The “Mirror” McCarty Keyhole During Transorbital Approach: An Anatomic Study With Surgical Implications
Authors: Corvino Sergio , Kassam Amin , Piazza Amedeo , Corrivetti Francesco , Esposito Felice , Iaconetta Giorgio , de Notaris Matteo
Published: July 2024

BACKGROUND AND OBJECTIVES:

McCarty keyhole (MCK) is the most important entry point during orbitocranial and cranio-orbital approaches; nevertheless, its anatomic coordinates have never been detailedly described from transorbital perspective. To provide the spatial coordinates for intraorbital projection of the “mirror” MCK by using the well-established main anatomic-surgical bony landmarks met along transorbital corridor.

METHODS:

MCK was identified in 15 adult dry skulls (30 sides) on exocranial surface of pterional region based on the well-defined external bony landmarks: on the frontosphenoid suture, 5 to 6 mm behind the joining point (JP) of frontozygomatic suture (FZS), frontosphenoid suture (FSS), and sphenozygomatic suture (SZS). A 1-mm burr hole was performed and progressively enlarged to identify the intracranial and intraorbital compartments. Exit site of the intraorbital part of burr hole was referenced to the FZS on the orbital rim, the superior orbital fissure, and the inferior orbital fissure and to the JP of FZS, FSS, and SZS. To electronically validate the results, 3-dimensional photorealistic and interactive models were reconstructed with photogrammetry. Finally, for a further validation, McCarty mirror keyhole was also exposed, based on results achieved, through endoscopic transorbital approach in 10 head specimens (20 sides).

RESULTS:

Intraorbital projection of MCK was identified on the FSS on intraorbital surface, 1.5 ± 0.5 mm posterior to JP, 11.5 ± 1.1 mm posterior to the FZS on orbital rim following the suture, 13.0 ± 1.2 mm from most anterior end of superior orbital fissure, 15.5 ± 1.4 mm from the most anterior end of the inferior orbital fissure in vertical line, on measurements under direct macroscopic visualization (mean ± SD). These values were electronically confirmed on the photogrammetric models with mean difference within 1 mm.

CONCLUSION:

To be aware of exact position of intraorbital projection of MCK during an early stage of transorbital approaches provides several surgical, clinical, and aesthetic advantages.
Hemifacial Spasm Associated With the Specific Offending Vein
Authors: Cao Chenglong , Li Mingwu , Wu Min , Jiang Xiaofeng
Published: July 2024

BACKGROUND AND OBJECTIVES:

Hemifacial spasm (HFS) caused by venous compression is a rare occurrence. Currently, there is no relevant research on the venous characteristics and potential pathogenic mechanisms causing venous HFS. Exploring the venous characteristics in venous-type HFS may reduce the likelihood of repeated surgery.

METHODS:

The authors presented 4 cases of HFS caused by veins of middle cerebellar peduncle (V. of Mid.Cer.Ped) successfully treated with microvascular decompression.

RESULTS:

Based on intraoperative observations and abnormal muscle response (AMR) monitoring, it was determined that V. of Mid.Cer.Ped were offending vessels in these patients. Moreover, veins crossed between the facial and vestibulocochlear nerves, and then surrounded the ventral aspect of the facial nerve root. Microvascular decompression for the offending vessel was successfully performed, and AMR disappeared for each patient. These patients were discharged without any complications and involuntary contractions or twitching of facial muscles.

CONCLUSION:

The study demonstrated that veins can indeed induce HFS. The characteristic of the V. of Mid.Cer.Ped that leads to HFS is that these veins traverse between the facial nerve and the vestibulocochlear nerve, and then surround the ventral aspect of the facial nerve root. The dynamic influence of cerebrospinal fluid leads to pulsatile impingement of the facial nerve on the vein, resulting in facial nerve bending and deformation at the location of the vein. Significantly, in the context of surgery, if it is noticed that the V. of Mid.Cer.Ped surrounds the ventral aspect of the facial nerve root and the facial nerve is compressed and deformed, when AMR disappears after decompression of the artery, it may be necessary to perform vein decompression.
Evolutionary conservation of VSX2 super-enhancer modules in retinal development
Authors: Honnell Victoria , Sweeney Shannon , Norrie Jackie , Parks Madison , Ramirez Cody , Jannu Asha Jacob , Xu Beisi , Teubner Brett , Lee Ah Young , Bell Claire , Dyer Michael A.
Published: July 2024

Super-enhancers (SEs) are expansive regions of genomic DNA that regulate the expression of genes involved in cell identity and cell fate. We recently identified developmental stage- and cell type-specific modules within the murine Vsx2 SE. Here, we show that the human VSX2 SE modules have similar developmental stage- and cell type-specific activity in reporter gene assays. By inserting the human sequence of one VSX2 SE module into a mouse with microphthalmia, eye size was rescued. To understand the function of these SE modules during human retinal development, we deleted individual modules in human embryonic stem cells and generated retinal organoids. Deleting one module results in small organoids, recapitulating the small-eyed phenotype of mice with microphthalmia, while deletion of the other module led to disruptions in bipolar neuron development. This prototypical SE serves as a model for understanding developmental stage- and cell type-specific effects of neurogenic transcription factors with complex expression patterns. Moreover, by elucidating the gene regulatory mechanisms, we can begin to examine how dysregulation of these mechanisms contributes to phenotypic diversity and disease.
Mechanical regulation of lymphocyte activation and function
Authors: Pathni Aashli , Wagh Kaustubh , Rey-Suarez Ivan , Upadhyaya Arpita
Published: July 2024

Mechanosensing, or how cells sense and respond to the physical environment, is crucial for many aspects of biological function, ranging from cell movement during development to cancer metastasis, the immune response and gene expression driving cell fate determination. Relevant physical stimuli include the stiffness of the extracellular matrix, contractile forces, shear flows in blood vessels, complex topography of the cellular microenvironment and membrane protein mobility. Although mechanosensing has been more widely studied in non-immune cells, it has become increasingly clear that physical cues profoundly affect the signaling function of cells of the immune system. In this Review, we summarize recent studies on mechanical regulation of immune cells, specifically lymphocytes, and explore how the force-generating cytoskeletal machinery might mediate mechanosensing. We discuss general principles governing mechanical regulation of lymphocyte function, spanning from the molecular scale of receptor activation to cellular responses to mechanical stimuli.
Clipping the Positive Lymph Node in Patients with Clinically Node Positive Breast Cancer Treated with Neoadjuvant Chemotherapy: Impact on Axillary Surgery in the ISPY-2 Clinical Trial
Authors: Switalla Kayla M. , Boughey Judy C. , Dimitroff Katrina , Yau Christina , Ladores Velle , Yu Hongmei , Tchou Julia , Golshan Mehra , Ahrendt Gretchen , Postlewait Lauren M. , Piltin Mara , Reyna Chantal R. , Matsen Cindy B. , Tuttle Todd M. , Wallace Anne M. , Arciero Cletus A. , Lee Marie Catherine , Tseng Jennifer , Son Jennifer , Rao Roshni , Sauder Candice , Naik Arpana , Howard-McNatt Marissa , Lancaster Rachael , Norwood Peter , Esserman Laura J. , Mukhtar Rita A.
Published: July 2024

Background

For patients with clinically node-positive (cN+) breast cancer undergoing neoadjuvant chemotherapy (NAC), retrieving previously clipped, biopsy-proven positive lymph nodes during sentinel lymph node biopsy [i.e., targeted axillary dissection (TAD)] may reduce false negative rates. However, the overall utilization and impact of clipping positive nodes remains uncertain.

Patients and Methods

We retrospectively analyzed cN+ ISPY-2 patients (2011–2022) undergoing axillary surgery after NAC. We evaluated trends in node clipping and associations with type of axillary surgery [sentinel lymph node (SLN) only, SLN and axillary lymph node dissection (ALND), or ALND only] and event-free survival (EFS) in patients that were cN+ on a NAC trial.

Results

Among 801 cN+ patients, 161 (20.1%) had pre-NAC clip placement in the positive node. The proportion of patients that were cN+ undergoing clip placement increased from 2.4 to 36.2% between 2011 and 2021. Multivariable logistic regression showed nodal clipping was independently associated with higher odds of SLN-only surgery [odds ratio (OR) 4.3, 95% confidence interval (CI) 2.8–6.8, p < 0.001]. This was also true among patients with residual pathologically node-positive (pN+) disease. Completion ALND rate did not differ based on clip retrieval success. No significant differences in EFS were observed in those with or without clip placement, both with or without successful clip retrieval [hazard ratio (HR) 0.85, 95% CI 0.4–1.7, p = 0.7; HR 1.8, 95% CI 0.5–6.0, p = 0.3, respectively].

Conclusion

Clip placement in the positive lymph node before NAC is increasingly common. The significant association between clip placement and omission of axillary dissection, even among patients with pN+ disease, suggests a paradigm shift toward TAD as a definitive surgical management strategy in patients with pN+ disease after NAC.
Επιδημιολογία και μορφολογική μελέτη των καταγμάτων του άνω πέρατος μηριαίου
Authors: Βλάχος Χρήστος
Published: July 2024

Η συχνότητα των καταγμάτων του εγγύς μηριαίου αυξάνεται ραγδαία, παρουσιάζοντας μια σημαντική πρόκληση για τα συστήματα υγείας παγκοσμίως και επιφέροντας σοβαρές κοινωνικές και οικονομικές επιπτώσεις. Ο κύριος στόχος αυτής της μελέτης ήταν να εντοπίσει πιθανούς διακριτικούς παράγοντες μεταξύ των καταγμάτων που συμβαίνουν στον αυχένα του μηριαίου και στην περιοχή των τροχαντήρων. Για το σκοπό αυτό, διεξήγαμε μια προοπτική μελέτη Κοορτής, που περιλάμβανε τόσο ακτινολογικές μετρήσεις, όσο και μετρήσεις με την μέθοδο της Διπλής Φωτονιακή Απορροφησιομέτρησης (DEXA), 70 ατόμων άνω των 65 ετών που εισήχθησαν στο Ορθοπαιδικό μας τμήμα με κάταγμα ισχίου και πληρούσαν τα κριτήρια εισαγωγής μας. Στο πρώτο μέρος της έρευνάς μας, καταγράψαμε το Μήκος του μηριαίου αυχένα, την Κεφαλοτροχαντήρια απόσταση, το Μήκος του άξονα του Ισχίου, την Αυχενοδιαφυσιακή γωνία, τη γωνία του Wiberg, τη γωνία Κλίσης της κοτύλης, τη Διάμετρο του μηριαίου αυχένα, τη διάμετρο της μηριαίας κεφαλής, τη Διάμετρο της μηριαίας διάφυσης, τη Διάμετρο του μηριαίου αυλού και την ταξινόμηση της οστεοαρθρίτιδας κατά Tonnis. Το δεύτερο μέρος περιλάμβανε την καταγραφή του T-score και της Πυκνότητας της Οστικής Μάζας (BMD) για το πάνω και κάτω μέρος του αυχένα του μηριαίου, της περιοχή των τροχαντήρων και της μηριαίας διάφυσης.Δεν παρατηρήθηκαν στατιστικά σημαντικές διαφορές κατά τη σύγκριση των επιλεγμένων παραμέτρων του εγγύς μηριαίου με τον τύπο του κατάγματος. Αυτό το εύρημα ήταν συνεπές με τις μεταβλητές όπως η ηλικία, το φύλο και η ταξινόμηση της οστεοαρθρίτιδας κατά Tonnis. Η αδυναμία της έρευνάς μας να καθορίσει διακριτικούς παράγοντες μεταξύ των καταγμάτων του αυχένα του μηριαίου και του τροχαντήρα υπογραμμίζει την ανάγκη για περαιτέρω μελέτες. Οι μελλοντικές έρευνες θα πρέπει όχι μόνο να ενσωματώνουν πιο ακριβείς τεχνικές αλλά και να πραγματοποιούν μια ολοκληρωμένη εξέταση που θα λαμβάνει υπόψη τόσο τα εσωτερικά όσο και τα εξωτερικά χαρακτηριστικά του εγγύς μηριαίου.