bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateral flow assay (LFA) in the diagnosis of COVID-19-associated pulmonary aspergillosis (CAPA): a single-center experience
Authors: Serin Istemi , Baltali Sevim , Cinli Tahir Alper , Goze Hasan , Demir Burçak , Yokus Osman
Published: November 2022

Background

Invasive pulmonary aspergillosis (IPA) is seen during coronavirus-2019 (COVID-19), has been reported in different incidences, and is defined as COVID-19-associated pulmonary aspergillosis (CAPA). Detection of galactomannan antigen is an important diagnostic step in diagnosing IPA. Enzyme-linked immunoassay (ELISA) is the most frequently used method, and lateral flow assay (LFA) is increasingly used with high sensitivity and specificity for rapid diagnosis. The present study aimed to compare the sensitivity of LFA and ELISA in the diagnosis of CAPA in COVID-19 patients followed in our hospital's ICU for pandemic (ICU-P).

Methods

This study included patients with a diagnosis of COVID-19 cases confirmed by polymerase chain reaction and were followed up in ICU-P between August 2021 and February 2022 with acute respiratory failure. The diagnosis of CAPA was based on the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology 2020 (ECMM/ ISHAM) guideline. Galactomannan levels were determined using LFA and ELISA in serum samples taken simultaneously from the patients.

Results

Out of the 174 patients followed in the ICU-P, 56 did not meet any criteria for CAPA and were excluded from the analysis. The rate of patients diagnosed with proven CAPA was 5.7% (10 patients). A statistically significant result was obtained with LFA for the cut-off value of 0.5 ODI in the diagnosis of CAPA (p < 0.001). The same significant statistical relationship was found for the cut-off value of 1.0 ODI for the ELISA (p < 0.01). The sensitivity of LFA was 80% (95% CI: 0.55–1.05, p < 0.05), specificity 94% (95% CI: 0.89–0.98, p < 0.05); PPV 53% (95% CI: 0.28–0.79, p > 0.05) and NPV was 98% (95% CI: 0.95–1.01, p < 0.05). The risk of death was 1.66 (HR: 1.66, 95% CI: 1.02–2.86, p < 0.05) times higher in patients with an LFA result of ≥ 0.5 ODI than those with < 0.5 (p < 0.05).

Conclusions

It is reckoned that LFA can be used in future clinical practice, particularly given its effectiveness in patients with hematological malignancies and accuracy in diagnosing CAPA.
Technology-free predictors of preterm birth in singleton women with threatened preterm labor: a prospective cohort study
Authors: Najjarzadeha Maryam , Mohammad-Alizadeh-Charandabi Sakineh , Abbasalizadeh Shamsi , Asghari-Jafarabadi Mohammad , Mirghafourvand Mojgan
Published: November 2022

Background

Prediction of preterm birth is still a challenge due to its multiple etiologies. This prospective cohort study aimed to determine the technology-free predictors of preterm birth in singleton women with threatened preterm labor.

Methods

This prospective cohort study was performed on 371 singleton women with gestational age of 23+ 6 to 36+ 4 weeks hospitalized for threatened preterm labor. The data were collected using a questionnaire including demographic characteristics, medical and maternal history, as well as the Perceived Stress Scale (PSS), the Multidimensional Scale of Perceived Social Support (MSPSS), and the WHO’s questionnaire of Violence against Women (VAW). The participants were followed-up until childbirth. The predictors were determined using multivariate logistic regression.

Results

Preterm birth occurred in 51% of women. Seven variables were determined as predictors; rupture of membranes [adjusted odds ratio 11.7, 95% confidence interval 5.4 to 25.6], cervical dilation [AOR 4.1, 95% CI 2.0 to 7.0], gravidity ≥6 [AOR 27.4, 95%CI 2.8 to 264.3], psychological violence during pregnancy [AOR 2.0, 95% CI 1.1 to 3.2], medical problems in pregnancy onset [AOR 1.7, 95% CI 1.1 to 2.8], vaginal bleeding/spotting [AOR 2.1, 95% CI 1.2 to 4.0] and woman age ≤ 19 [AOR 2.2, 95% CI 1.1 to 4.5]. The proportion of variance explained by all these factors was 33.6%.

Conclusions

The technology-free factors seems to have moderate power in preterm birth prediction in singleton pregnant women hospitalized for threatened preterm labor. However, these results are discoveries without verification or validation and need to be confirmed by generalizable studies.
Comparison of surgical outcomes with and without Ologen collagen matrix augmentation during XEN gel stent implantation
Authors: Park Jimin , Shin Joong Won , Sung Kyung Rim
Published: November 2022

Background

To compare the surgical outcomes and postoperative complications with and without Ologen collagen matrix augmentation during XEN gel stent implantation.

Methods

We retrospectively analyzed patients who underwent XEN gel stent implantation with an ab externo technique. The amount of intraocular pressure (IOP) reduction, percentage of postoperative complications and additional management, and surgical success defined as IOP reduction greater than 20% compared with the preoperative IOP measurement were compared between Ologen-augmented and non-augmented groups. Groups of patients who underwent XEN gel stent implantation alone and combined with phacoemulsification were analyzed separately.

Results

A total 103 eyes of 103 participants were included. Of those, 72 eyes underwent standalone XEN gel stent implantation: 42 eyes with Ologen augmentation (Oloxen group) and 30 eyes without Ologen augmentation (Xen group). Thirty-one eyes underwent XEN gel stent implantation with phacoemulsification: 19 eyes with Ologen augmentation (Phaco-Oloxen group) and 12 eyes without Ologen augmentation (PhacoXen group). The surgical success rate at six months postoperatively was not different between the Oloxen and Xen groups (56.4% vs 43.3%, P > 0.05) or between the Phaco-Oloxen group and PhacoXen group (57.9% vs 41.7%, P > 0.05). The prevalence of postoperative hypotony, 5-fluorouracil injections, use of anti-glaucoma medications, bleb needling, and additional glaucoma surgeries was not different between the Oloxen and Xen groups or between the Phaco-Oloxen and PhacoXen groups when assessed six months postoperatively.

Conclusions

All groups showed significant IOP reduction after XEN gel stent implantation, but there was no significant difference between the Ologen collagen matrix augmented and non-augmented groups in surgical outcomes.
Vitamin D levels among children, adolescents, adults, and elders in Pakistani population: a cross-sectional study
Authors: Arshad Saba , Zaidi Syed Jaffar Abbas
Published: November 2022

Background

Vitamin D is not only an essential part of a healthy diet but it is also known as the sunshine hormone. It helps to absorb calcium and phosphate within the body and is essential for the development of teeth and bones in growing children. Deficiency in vitamin D causes weak bones, osteoporosis in older individuals, and osteomalacia in children. It also causes loss of alveolar bone around the teeth, increased dental cavities, and other problems associated with gum disease. It can cause depression, fatigue, and appetite loss. This study aims to observe vitamin D deficiency, insufficiency, and sufficiency among children, adults, adolescents, and elders in the Pakistani population.

Methods

A cross-sectional survey was conducted with 27,880 individuals referred from the general out-patient-department (OPD) to Dow Diagnostic Research and Reference Laboratory (DDRRL) units at Dow University of Health Sciences (DUHS) Karachi, Pakistan, for a period of three months from January to March 2017. They were examined for laboratory findings of serum 25 hydroxyvitamin D levels to determine vitamin D deficiency, insufficiency, and sufficiency among all age groups of both male and female genders.

Results

A total of 26,750 individuals with a mean age of 38 ± 18 years were statistically examined for laboratory findings of serum vitamin D levels. Vitamin D deficiency was observed in 56% of individuals with a mean log of 1.01 ± 0.18 ng/ml serum vitamin D levels, vitamin D insufficiency in 20% of individuals with a mean log of 1.38 ± 0.05 ng/ml serum vitamin D levels and vitamin D sufficiency in 24% individuals with a mean log of 1.63 ± 0.12 ng/ml serum vitamin D levels. The highest percentage of individuals deficient in vitamin D were children and adolescents of age ranging between 6 to 18 years.

Conclusion

The findings of vitamin D deficiency in children and adolescents direct higher authorities in the public health sector to take immediate steps to screen, intervene and educate high-risk populations incorporating vitamin D supplements to establish preventive and therapeutic measures.
Comparison of supervised exercise therapy with or without biopsychosocial approach for chronic nonspecific low back pain: a randomized controlled trial
Authors: Hrkać Antonija , Bilić Darko , Černy-Obrdalj Edita , Baketarić Ivan , Puljak Livia
Published: November 2022

Background

A biopsychosocial rehabilitation is recommended for chronic nonspecific low back pain (CNLBP); however, its effectiveness compared to the traditional supervised exercise therapy of CNLBP treatment is still unclear.

Methods

This was a parallel-group randomized controlled clinical trial. The sample consisted of 180 participants of both sexes, aged ≥18 years, with CNLBP for ≥3 months. Using web randomization and concealed allocation, they were assigned to three groups; graded activity receiving cognitive-behavioral therapy, group-based combined exercise therapy and education (GA; n = 59), supervised group-based combined exercise therapy and education (SET; n = 63), and a control group receiving usual care (n = 58). Interventions were administered for 4 weeks (8 sessions). The primary outcome was pain intensity. Outcome measures were collected baseline, after interventions (4 weeks), and during two follow-up periods (3 and 6 months).

Results

After the intervention, GA had a significant large effect on pain reduction compared to the control group (MD of 22.64 points; 95% CI = 16.10 to 29.19; p < 0.0001; Cohen’s d = 1.70), as well as SET compared with the control group (MD of 21.08 points; 95% CI = 14.64 to 27.52; p < 0.0001; Cohen’s d = 1.39), without significant difference between two intervention groups. At 3 and 6 months of follow-up, GA had a statistically significantly better effect in reducing pain, disability and fear-avoidance beliefs, and improving spinal extensor endurance, range of extension and quality of life compared to SET and the control group. A statistically significantly better effect of SET compared with the control group was found in reducing pain, disability, fear-avoidance beliefs, and improving the physical component of quality of life. Harms were not reported.

Conclusion

This study suggests that graded activity and group-based supervised exercise therapy have beneficial effects over the control group in the treatment of CNLBP. The graded activity was more beneficial than supervised group-based exercise therapy only during the follow-up.

Trial registration

Clinicaltrials.gov (NCT04023162; registration date: 17/07/2019).
Chondromalacia patella increases the risk of herpes zoster: a population-based study
Authors: Chen Chia-Hung , Cheng Yung-Chi , Yang Hsin-Yi , Tsai Ching-Fang , Hsu Chao-Yu , Ke Der-Shin , Hsieh Wen-Che
Published: November 2022

Background

The reactivation of herpes zoster (HZ) is associated with disease stress. However, the relationship between chondromalacia patella (CMP) and HZ remains poorly understood. This study investigated the relationship between CMP and the risk of developing HZ.

Methods

Data were collected from the Taiwan’s National Health Insurance Research Database. Patients with CMP diagnosed between 2000 and 2017 were assigned to the case group; patients without CMP were randomly selected from the same database and paired with controls matched by age and sex. The primary outcome was a diagnosis of HZ. All patients were followed until their diagnosis of HZ, their withdrawal from the NHI program, their death, or the end of 2017, whichever was earliest. The risk of developing HZ was compared between the case and control groups.

Results

In total, 22,710 patients with CMP and 90,840 matched controls were enrolled. The overall incidence rates of HZ in the CMP and control cohorts were 7.94 and 7.35 per 1,000 person-years, respectively. After potential confounders were controlled for, the case group exhibited a higher risk of HZ than did the control group [adjusted hazard ratio (aHR) = 1.06, p < 0.05]. In a stratification analysis by age, patients over 65 years old in the CMP group exhibited a higher risk of HZ than did those in the control group (aHR = 1.22, p < 0.01). In a stratification analysis by sex, women with CMP were at greater risk of developing HZ than women without CMP (aHR = 1.18, p < 0.01).

Conclusion

Patients with CMP, especially elder adults and women, exhibited a higher risk of HZ. The HZ risk of patients with CMP should thus be assessed, and the necessity of HZ vaccination should be informed.
False certainty in the acquisition of anatomical and physiotherapeutic knowledge
Authors: von Hoyer Johannes , Bientzle Martina , Cress Ulrike , Grosser Johannes , Kimmerle Joachim , Peter Holtz
Published: November 2022

Background

Efficient metacognitive monitoring, that is the monitoring of one’s own thought processes and specifically one’s state of knowledge, is essential for effective clinical reasoning. Knowing what one does and does not know is a competency that students of health professions need to develop. Students often tend to develop false certainty in their own knowledge in the longer course of their education, but the time frame that is required for this effect to occur has remained unclear. We investigated whether students developed false certainty already after one course unit.

Methods

This study analysed data from one sample of medical students and four samples of physiotherapy students in two formal educational settings (total N = 255) who took knowledge tests before and after a course unit. We examined changes in students’ confidence separately for correctly and incorrectly answered questions and analysed their ability to assign higher levels of confidence to correct answers than to incorrect answers (discrimination ability).

Results

Students’ knowledge as well as confidence in their correct answers in knowledge tests increased after learning. However, consistently for all samples, confidence in incorrect answers increased as well. Students’ discrimination ability improved only in two out of the five samples.

Conclusions

Our results are in line with recent research on confidence increase of health professions students during education. Extending those findings, our study demonstrated that learning in two different formal educational settings increased confidence not only in correct but also in incorrect answers to knowledge questions already after just one learning session. Our findings highlight the importance of improving metacognition in the education of health professionals—especially their ability to know what they do not know.
Effect of different teaching/learning approaches using virtual patients on student’s situational interest and cognitive load: a comparative study
Authors: Fuoad Sura Ali , El-Sayed Walid , Marei Hesham
Published: November 2022

Background

Virtual Patients (VPs) have been receiving considerable attention in medical education as an authentic learning and teaching approach. The study aimed to evaluate the effect of using different approaches of conduction of virtual patients (VPs) on students’ cognitive load and situational interest.

Methods

The study is an experimental study. Two different cohorts have participated during the academic year 2019/2020 and 2020/2021. The first cohort (Group 1) was exposed to a lecture followed by an independent VPs session, and the second cohort (Group 2) was exposed to a collaborative VPs session. The situational interest and Cognitive load were compared between the two groups. All sessions are about one topic related to maxillofacial trauma.

Results

Findings showed that there was no significant difference between the median score of the situational interest at repeated time points during the Collaborative VPs (Group 2). However, in group 1, there was a significant difference between the median score of situational interest at repeated time points during independent VPs where the lowest score was found to be at the end of the session. Also, results showed that the collaborative VPs (Group 2) showed a high median score of situational interest than both lecture and independent VPs (Group 1). Furthermore, the study showed that there is no significant difference in the intrinsic cognitive load among the three sessions. However, the extraneous cognitive load was low in collaborative VPs (Group 2) than in both lecture and independent VPs sessions (Group 1).

Conclusion

The use of VPs in a collaborative interactive learning activity is more effective than its use as an independent learning activity in enhancing students’ situational interest and reducing cognitive load. However, giving independent VPs after the lecture with the same topic is considered a limitation of the study as this can affect the situational interest of the students by filling their gab of knowledge.
‘A life in a day’ simulation experience: perceptions of oncology nurses and pharmacy staff
Authors: Ehibhatiomhan Rachel , Foreman Emma , Barrott Lisa , Shek Jessica , Nabhani-Gebara Shereen
Published: November 2022

Background

Due to an increase in patient numbers, more cancer patients are being reviewed by non-medical healthcare professionals (HCPs), and it is essential that they can empathise with patients and care for them holistically. ‘A Life in a Day’ is a role reversal simulation (RRS) which demonstrates the challenges, choices and impacts that cancer patients face every day, facilitated by a Smartphone application (app). This study focused on renal cell carcinoma (RCC) and was designed to evaluate the impact of RRS on participants from the British Oncology Pharmacy Association (BOPA) and the UK Oncology Nursing Society (UKONS), and identify any changes made to clinical practice as a result.

Method

A survey was conducted via the app before and after the experience. Individual semi-structured interviews were conducted with participants over Microsoft Teams.

Results

Data from the survey showed that after the experience 97% of all participants strongly agreed that they ‘feel empathy for RCC patients’ and 90% strongly agreed that they ‘feel inspired to place patients at the centre of their work’. There were 5 themes extrapolated from the qualitative data: Holistic understanding of Patients, Reflections on Practice, Changes in Practice, Outreach to Colleagues, Education & Training.

Conclusion

Participants reported an increase in empathy for their patients which inspired them to make changes to their practice. This involved being more holistic in their care and taking on more responsibility. They recommended use of RRS for HCP training and continued professional development. They also suggested incorporation of RRS into the pharmacy undergraduate curriculum.
Comparison between immunotherapy efficacy in early non-small cell lung cancer and advanced non-small cell lung cancer: a systematic review
Authors: Wang Yimin , Li Chuling , Wang Zimu , Wang Zhaofeng , Wu Ranpu , Wu Ying , Song Yong , Liu Hongbing
Published: November 2022

Background

Currently, immunotherapy is widely used in the treatment of various stages of non-small cell lung cancer. According to clinical experience and results of previous studies, immunotherapy as neoadjuvant therapy seems to exhibit better efficacy against early resectable non-small cell lung cancer as compared to advanced lung cancer, which is often defined as unresectable non-small cell lung cancer. However, this observation has not been established in clinical studies. This systematic review aimed to evaluate the efficacy of immunotherapy in early and late lung cancer, wherein objective response rate (ORR) and disease control rate (DCR) were used as evaluation indexes. The present study also evaluated the safety of immunotherapy in early and late lung cancer, wherein the rate of treatment-related adverse reactions (TRAEs) was used as an indicator.

Methods

Electronica databases, including PubMed, Cochrane Library, Embase, and other databases, were searched to identify relevant studies. Besides this, all the available reviews, abstracts, and meeting reports from the main international lung cancer meetings were searched manually. ORR, DCR, and TRAEs were extracted as the primary outcomes.

Results

A total of 52 randomized controlled trials involving 13,660 patients were shortlisted. It was observed that immunotherapy alone significantly improved DCR in early lung cancer in comparison to advanced lung cancer. Importantly, the improvement in ORR was not to the same extent as reported in the case of advanced lung cancer. The combination of immunotherapy with other therapies, especially immunochemotherapy, significantly improved ORR and DCR in early lung cancer. In terms of safety, immunotherapy either alone or in combination with other therapies exhibited a better safety profile in early lung cancer than in advanced lung cancer.

Conclusions

Altogether, the benefits of immunotherapy in early lung cancer appeared to be better than those observed in advanced lung cancer, especially with the regard to the regimen of immunotherapy in combination with chemotherapy. In terms of safety, both immunotherapy alone and its combination with chemotherapy were found to be safer in early lung cancer as compared to advanced lung cancer.
Childhood diabetes mellitus and early-onset kidney diseases later in life: a nationwide population-based matched cohort study
Authors: Sun Jiahong , Wang Ce , Zhao Min , Lee Priscilla M. Y. , Xi Bo , Yu Yongfu , Li Jiong
Published: November 2022

Background

The empirical evidence remains inconclusive for an association between diabetes mellitus (DM) in children and early-onset kidney disease later in life, and little is known about the effects of DM types (i.e., type 1 diabetes [T1DM] and type 2 diabetes [T2DM]) in childhood on type-specific kidney diseases. We aimed to evaluate the association of childhood DM with overall and type-specific early-onset kidney diseases later in life.

Methods

The population-based matched cohort study included 9356 individuals with DM (T1DM: 8470, T2DM: 886) diagnosed in childhood (< 18 years) who were born between 1977 and 2016, and 93,560 individuals without DM matched on sex and year of birth in Denmark. The main outcomes were overall and type-specific early-onset kidney diseases. The follow-up period of all included participants was from the date of DM diagnosis in the exposure group until the first diagnosis of kidney disease, emigration, or 31 December 2018, whichever came first.

Results

During a median follow-up of 13 years, children with DM had a 154% increased risk of early-onset kidney diseases than children without DM (adjusted hazard ratios 2.54, 95% confidence intervals 2.38–2.72), and T1DM (2.48, 2.31–2.67) and T2DM (2.75, 2.28–3.31) showed similar results. Children with DM also had a higher risk of multiple specific kidney diseases including glomerular diseases, renal tubulo-interstitial diseases, renal failure, and urolithiasis. The risks of type-specific kidney diseases including glomerular diseases and renal failure tended to be higher for children with T2DM (glomerular diseases: 5.84, 3.69–9.24; renal failure: 14.77, 8.53–25.59) than those with T1DM (glomerular diseases: 3.14, 2.57–3.83; renal failure: 8.24, 6.66–10.20).

Conclusions

Children with DM had a higher increased risk of early-onset overall and specific kidney diseases later in life. Early prevention and treatment of both T1DM and T2DM in childhood may significantly reduce the risk of kidney diseases later in life.
A review on the role of mir-16-5p in the carcinogenesis
Authors: Ghafouri-Fard Soudeh , Khoshbakht Tayyebeh , Hussen Bashdar Mahmud , Abdullah Sara Tharwat , Taheri Mohammad , Samadian Mohammad
Published: November 2022

miR-16-5p is microRNA with important roles in the development of diverse malignancies including neuroblastoma, osteosarcoma, hepatocellular carcinoma, cervical cancer, breast cancer, brain tumors, gastrointestinal cancers, lung cancer and bladder cancer. This miRNA has 22 nucleotides. hsa-miR-16-5p is produced byMIR16-1gene. First evidence for its participation in the carcinogenesis has been obtained by studies reporting deletion and/or down-regulation of these miRNAs in chronic lymphocytic leukemia. Subsequent studies have shown down-regulation of miR-16-5p in a variety of cancer cell lines and clinical samples. Besides, tumor suppressor role of miR-16-5p has been verified in animal models of different types of cancers. Studies in these models have shown that over-expression of this miRNA or modulation of expression of lncRNAs that sponge this miRNA can block carcinogenic processes. In the current review, we summarize function of miR-16-5p in the development and progression of different cancers.
The function of prohibitins in mitochondria and the clinical potentials
Authors: Oyang Linda , Li Jian , Jiang Xianjie , Lin Jinguan , Xia Longzheng , Yang Lixia , Tan Shiming , Wu Nayiyuan , Han Yaqian , Yang Yiqing , Luo Xia , Li Jinyun , Liao Qianjin , Shi Yingrui , Zhou Yujuan
Published: November 2022

Prohibitins (PHBs) are a class of highly evolutionarily conserved proteins that widely distribute in prokaryotes and eukaryotes. PHBs function in cell growth and proliferation or differentiation, regulating metabolism and signaling pathways. PHBs have different subcellular localization in eukaryotes, but they are mainly located in mitochondria. In the mitochondria, PHBs stabilize the structure of the mitochondrial membrane and regulate mitochondrial autophagy, mitochondrial dynamics, mitochondrial biogenesis and quality control, and mitochondrial unfolded protein response. PHBs has shown to be associated with many diseases, such as mitochondria diseases, cancers, infectious diseases, and so on. Some molecule targets of PHBs can interfere with the occurrence and development of diseases. Therefore, this review clarifies the functions of PHBs in mitochondria, and provides a summary of the potential values in clinics.
Intracellular and extracellular factors of colorectal cancer liver metastasis: a pivotal perplex to be fully elucidated
Authors: Niu Yaru , Yang Wenwei , Qian Haili , Sun Yongkun
Published: November 2022

Metastasis is the leading cause of death in colorectal cancer (CRC) patients, and the liver is the most common site of metastasis. Tumor cell metastasis can be thought of as an invasion-metastasis cascade and metastatic organotropism is thought to be a process that relies on the intrinsic properties of tumor cells and their interactions with molecules and cells in the microenvironment. Many studies have provided new insights into the molecular mechanism and contributing factors involved in CRC liver metastasis for a better understanding of the organ-specific metastasis process. The purpose of this review is to summarize the theories that explain CRC liver metastasis at multiple molecular dimensions (including genetic and non-genetic factors), as well as the main factors that cause CRC liver metastasis. Many findings suggest that metastasis may occur earlier than expected and with specific organ-anchoring property. The emergence of potential metastatic clones, the timing of dissemination, and the distinct routes of metastasis have been explained by genomic studies. The main force of CRC liver metastasis is also thought to be epigenetic alterations and dynamic phenotypic traits. Furthermore, we review key extrinsic factors that influence CRC cell metastasis and liver tropisms, such as pre-niches, tumor stromal cells, adhesion molecules, and immune/inflammatory responses in the tumor microenvironment. In addition, biomarkers associated with early diagnosis, prognosis, and recurrence of liver metastasis from CRC are summarized to enlighten potential clinical practice, including some markers that can be used as therapeutic targets to provide new perspectives for the treatment strategies of CRC liver metastasis.
Neighborhood environmental factors linked to hospitalizations of older people for viral lower respiratory tract infections in Spain: a case-crossover study
Authors: Álvaro-Meca Alejandro , Sepúlveda-Crespo Daniel , Resino Rosa , Ryan Pablo , Martínez Isidoro , Resino Salvador
Published: November 2022

Background

Lower respiratory tract viral infection (LRTI) is a significant cause of morbidity-mortality in older people worldwide. We analyzed the association between short-term exposure to environmental factors (climatic factors and outdoor air pollution) and hospital admissions with a viral LRTI diagnosis in older adults.

Methods

We conducted a bidirectional case-crossover study in 6367 patients over 65 years of age with viral LRTI and residential zip code in the Spanish Minimum Basic Data Set. Spain’s State Meteorological Agency was the source of environmental data. Associations were assessed using conditional logistic regression. P-values were corrected for false discovery rate (q-values).

Results

Almost all were hospital emergency admissions (98.13%), 18.64% were admitted to the intensive care unit (ICU), and 7.44% died. The most frequent clinical discharge diagnosis was influenza (90.25%). LRTI hospital admissions were more frequent when there were lower values of temperature and O3 and higher values of relative humidity and NO2. The regression analysis adjusted by temperatures and relative humidity showed higher concentrations at the hospital admission for NO2 [compared to the lag time of 1-week (q-value< 0.001) and 2-weeks (q-value< 0.001)] and O3 [compared to the lag time of 3-days (q-value< 0.001), 1-week (q-value< 0.001), and 2-weeks (q-value< 0.001)] were related to a higher odds of hospital admissions due to viral LRTI. Moreover, higher concentrations of PM10 at the lag time of 1-week (q-value = 0.023) and 2-weeks (q-value = 0.002), and CO at the lag time of 3-days (q-value = 0.023), 1-week (q-value< 0.001) and 2-weeks (q-value< 0.001)], compared to the day of hospitalization, were related to a higher chances of hospital admissions with viral LRTI.

Conclusion

Unfavorable environmental factors (low temperatures, high relative humidity, and high concentrations of NO2, O3, PM10, and CO) increased the odds of hospital admissions with viral LRTI among older people, indicating they are potentially vulnerable to these environmental factors.

Graphical Abstract
Vascular endothelial growth factor and the risk of venous thromboembolism: a genetic correlation and two-sample Mendelian randomization study
Authors: Zhang Qiaoyun , Zhang Xiaoyu , Zhang Jie , Wang Biyan , Tian Qiuyue , Meng Xiaoni , Zhang Jinxia , Jiang Mengyang , Zhang Yiqiang , Zheng Deqiang , Wu Lijuan , Wang Wei , Wang Baoguo , Wang Youxin
Published: November 2022

Background

The relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE.

Methods

Summary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score regression (LDSC) and five robust MR analytical approaches were conducted to estimate the genetic correlations and causal inference. The MR-Egger intercept, Cochran’s Q, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on outcomes. Notably, replication analyses were performed using different subgroups of VTE.

Results

LDSC failed to identify genetic correlations between VEGF and VTE. Based on 9 SNPs, the circulating VEGF level was positively related to the risk of VTE using inverse variance weighting (IVW) method (odds ratio (OR) = 1.064, 95% confidence interval (CI), 1.009–1.122). Reverse MR analyses showed that genetic liability for VTE was not associated with increased VEGF level (β = -0.021, 95% CI, -0.087-0.045). Pleiotropy-robust methods indicated no bias in any estimates.

Conclusions

Our findings failed to detect coheritability between VEGF and VTE. The suggestive positive effect of the higher VEGF level on the VTE risk may have clinical implications, suggesting that VEGF as a possible predictor and therapeutic target for VTE prevention need to be further warranted.
Elevation of spermine remodels immunosuppressive microenvironment through driving the modification of PD-L1 in hepatocellular carcinoma
Authors: Shi Hong-Xiang , Liang Chao , Yao Chao-Yan , Gao Zi-Xuan , Qin Jia , Cao Jin-Lan , Zhang Ming-Zhu , Li Ying-Ying , Wang Meng-Qing , Sun Hua , Xie Song-Qiang , Fang Dong
Published: November 2022

Background

Spermine is frequently elevated in tumor tissues and body fluids of cancer patients and is critical for cancer cell proliferation, migration and invasion. However, the immune functions of spermine in hepatocellular carcinoma progression remains unknown. In the present study, we aimed to elucidate immunosuppressive role of spermine in hepatocellular carcinoma and to explore the underlying mechanism.

Methods

Whole-blood spermine concentration was measured using HPLC. Human primary HCC tissues were collected to examine the expression of CaSR, p-Akt, β-catenin, STT3A, PD-L1, and CD8. Mouse model of tumorigenesis and lung metastasis were established to evaluate the effects of spermine on hepatocellular carcinoma. Western blotting, immunofluorescence, real time PCR, digital Ca2+ imaging, and chromatin immunoprecipitation assay were used to investigate the underlying mechanisms by which spermine regulates PD-L1 expression and glycosylation in hepatocellular carcinoma cells.

Results

Blood spermine concentration in the HCC patient group was significantly higher than that in the normal population group. Spermine could facilitate tumor progression through inducing PD-L1 expression and decreasing the CD8+ T cell infiltration in HCC. Mechanistically, spermine activates calcium-sensing receptor (CaSR) to trigger Ca2+ entry and thereby promote Akt-dependent β-catenin stabilization and nuclear translocation. Nuclear β-catenin induced by spermine then activates transcriptional expression of PD-L1 and N-glycosyltransferase STT3A, while STT3A in turn increases the stability of PD-L1 through inducing PD-L1 protein N-glycosylation in HCC cells.

Conclusions

This study reveals the crucial function of spermine in establishing immune privilege by increasing the expression and N-glycosylation of PD-L1, providing a potential strategy for the treatment of hepatocellular carcinoma.
Promotion of a synthetic degradation of activated STAT6 by PARP-1 inhibition: roles of poly(ADP-ribosyl)ation, calpains and autophagy
Authors: Wang Jeffrey , Ghonim Mohamed A. , Ibba Salome V. , Luu Hanh H. , Aydin Yucel , Greer Peter A. , Boulares A. Hamid
Published: November 2022

Background

We reported that PARP-1 regulates genes whose products are crucial for asthma, in part, by controlling STAT6 integrity speculatively through a calpain-dependent mechanism. We wished to decipher the PARP-1/STAT6 relationship in the context of intracellular trafficking and promoter occupancy of the transcription factor on target genes, its integrity in the presence of calpains, and its connection to autophagy.

Methods

This study was conducted using primary splenocytes or fibroblasts derived from wild-type or PARP-1−/− mice and Jurkat T cells to mimic Th2 inflammation.

Results

We show that the role for PARP-1 in expression of IL-4-induced genes (e.g. gata-3) in splenocytes did not involve effects on STAT6 phosphorylation or its subcellular trafficking, rather, it influenced its occupancy of gata-3 proximal and distal promoters in the early stages of IL-4 stimulation. At later stages, PARP-1 was crucial for STAT6 integrity as its inhibition, pharmacologically or by gene knockout, compromised the fate of the transcription factor. Calpain-1 appeared to preferentially degrade JAK-phosphorylated-STAT6, which was blocked by calpastatin-mediated inhibition or by genetic knockout in mouse fibroblasts. The STAT6/PARP-1 relationship entailed physical interaction and modification by poly(ADP-ribosyl)ation independently of double-strand-DNA breaks. Poly(ADP-ribosyl)ation protected phosphorylated-STAT6 against calpain-1-mediated degradation. Additionally, our results show that STAT6 is a bonafide substrate for chaperone-mediated autophagy in a selective and calpain-dependent manner in the human Jurkat cell-line. The effects were partially blocked by IL-4 treatment and PARP-1 inhibition.

Conclusions

The results demonstrate that poly(ADP-ribosyl)ation plays a critical role in protecting activated STAT6 during Th2 inflammation, which may be synthetically targeted for degradation by inhibiting PARP-1.
HiTIMED: hierarchical tumor immune microenvironment epigenetic deconvolution for accurate cell type resolution in the tumor microenvironment using tumor-type-specific DNA methylation data
Authors: Zhang Ze , Wiencke John K. , Kelsey Karl T. , Koestler Devin C. , Christensen Brock C. , Salas Lucas A.
Published: November 2022

Background

Cellular compositions of solid tumor microenvironments are heterogeneous, varying across patients and tumor types. High-resolution profiling of the tumor microenvironment cell composition is crucial to understanding its biological and clinical implications. Previously, tumor microenvironment gene expression and DNA methylation-based deconvolution approaches have been shown to deconvolve major cell types. However, existing methods lack accuracy and specificity to tumor type and include limited identification of individual cell types.

Results

We employed a novel tumor-type-specific hierarchical model using DNA methylation data to deconvolve the tumor microenvironment with high resolution, accuracy, and specificity. The deconvolution algorithm is namedHiTIMED. Seventeen cell types from three major tumor microenvironment components can be profiled (tumor, immune, angiogenic) byHiTIMED, and it provides tumor-type-specific models for twenty carcinoma types. We demonstrate the prognostic significance of cell types that other tumor microenvironment deconvolution methods do not capture.

Conclusion

We developedHiTIMED, a DNA methylation-based algorithm, to estimate cell proportions in the tumor microenvironment with high resolution and accuracy.HiTIMEDdeconvolution is amenable to archival biospecimens providing high-resolution profiles enabling to study of clinical and biological implications of variation and composition of the tumor microenvironment.
Molecular characteristics of norovirus in sporadic and outbreak cases of acute gastroenteritis and in sewage in Sichuan, China
Authors: Cao Ranran , Ma Xiaozhen , Pan Ming
Published: November 2022

Background

Norovirus is highly diverse and constant surveillance is essential for the prevention and control of norovirus gastroenteritis.

Methods

From 2015 to 2019, fecal samples were collected from sporadic cases and outbreaks of acute gastroenteritis reported to Sichuan center for disease control and prevention. Sewage samples were collected from a wastewater treatment plant in Sichuan. All samples were tested for norovirus by real-time reverse transcription polymerase chain reaction. Norovirus-positive clinical samples were sequenced by Sanger sequencing. Sewage samples were sequenced by amplicon and virome sequencing.

Results

A total of 1462 fecal samples were collected and 11 different norovirus genotypes were detected. GII.4 Sydney 2012[P31] and GII.3[P12] were the dominant genotypes in sporadic cases whereas GII.2[P16] and GII.17[P17] were the dominant genotypes in outbreaks. GII.3 was predominant in children 0–6 months of age during spring and summer, while GII.4 was predominant in children older than 6 months and in the autumn. The detection rate of GII.17[P17] increased with age. In sewage, 16 genotypes were detected. GII.3, GII.4, GI.1, and GI.2 were the dominant genotypes.

Conclusion

This study demonstrated that multiple norovirus genotypes co-circulate in Sichuan. It is vital to continuously trace the genetic diversity of norovirus to give a future perspective on surveillance needs and guide vaccine design and policy decisions.
The perioperative outcomes of uniport versus two-port and three-port video-assisted thoracoscopic surgery in lung cancer: a systematic review and meta-analysis
Authors: Cheng Ya-Fu , Huang Chang-Lun , Hung Wei-Heng , Cheng Ching-Yuan , Wang Bing-Yen
Published: November 2022

Background

Uniport video-assisted thoracoscopic surgery (VATS) has been applied widely for the treatment of lung cancer in recent years. Some studies have reported that uniport VATS might provide better outcomes than multiport VATS. However, the perioperative outcomes of uniport VATS compared with two-port and three-port VATS, respectively, have yet to be studied at a comprehensive scale. This meta-analysis study compares the perioperative efficacy among uniport, two-port, and three-port VATS.

Methods

We searched studies published before October 1, 2019, by using Web of Science databases, Ovid Medline, Embase, and PubMed. Studies that compared uniport VATS with two-port or three-port VATS for patients with lung cancer were included. Operative time, perioperative blood loss, number of lymph nodes retrieved, conversion rate, duration of postoperative chest tube drainage, length of hospital stay (LoS), visual analogue pain scores on postoperative day (POD) 1 and POD 3, and overall morbidity were evaluated.

Results

Sixteen studies that compared uniport VATS with two-port or three-port VATS in the treatment of lung cancer were included. Uniport VATS showed less blood loss, a shorter duration of postoperative drainage and a lower visual analogue pain score on POD 3 than two-port VATS; it showed a shorter duration of postoperative drainage, a shorter LoS, and lower visual analogue pain scores on POD 1 and POD 3 than three-port VATS. There were no significant differences in the number of lymph nodes retrieved, operative time, conversion rate, and overall morbidity rate when comparing uniport VATS with two-port VATS or three-port VATS.

Conclusions

Uniport VATS might provide better perioperative outcomes than either two-port or three-port VATS in lung cancer treatment.
The actual status of drug prices and adjustment factors for drug price calculation: an analysis of ultra-orphan drug development in Japan
Authors: Kawakami Akihiko , Masamune Ken
Published: November 2022

Background

Extremely high prices facilitate drug development for ultra-rare diseases (ultra-orphan drugs). However, various problems arise in terms of healthcare financing and fairness, and the status of ultra-orphan drug pricing remains ambiguous. In this study, we investigated ultra-orphan drug prices in Japan relative to that of other drugs. We examined the relationship between annual expected drug prices and expected sales, and the expected number of patients, for 393 drugs containing new active ingredients for therapeutic use that were listed on the National Health Insurance drug price list in Japan between April 16, 2010 and August 26, 2020. In addition, we compared prices, the drug price calculation method, and price calculation adjustment factors for ultra-orphan and other drugs.

Results

Drug prices tended to increase as the expected number of patients to whom the drug was administered decreased; however, this trend diminished when the expected number of patients was less than 1000. On the other hand, the expected sales tended to decrease as the number of expected patients decreased, and this tendency was reinforced when the expected number of patients was less than 1000. The cost accounting method tended to be used for the price calculation of ultra-orphan drugs, but there were no price differences based on the drug price calculation method. Regarding the price calculation adjustment factors, the premium for usefulness tended to be higher for ultra-orphan drugs. The premium for marketability was higher for non-orphan drugs but did not differ from that for orphan drugs, except for ultra-orphan drugs.

Conclusions

The status of drug prices and expected sales differed beyond a threshold of 1000 expected patients, indicating that recovering the development cost for ultra-orphan drugs is difficult. In addition, the higher premium for usefulness for ultra-orphan drugs reflects the largely unmet need of the associated diseases. Scarcity among orphan drugs is not considered for marketability, highlighting the need for a new framework to promote the development of ultra-orphan drugs.
Natural killer cells in clinical development as non-engineered, engineered, and combination therapies
Authors: Lamers-Kok Nina , Panella Denise , Georgoudaki Anna-Maria , Liu Haiping , Özkazanc Didem , Kučerová Lucia , Duru Adil Doganay , Spanholtz Jan , Raimo Monica
Published: November 2022

Natural killer (NK) cells are unique immune effectors able to kill cancer cells by direct recognition of surface ligands, without prior sensitization. Allogeneic NK transfer is a highly valuable treatment option for cancer and has recently emerged with hundreds of clinical trials paving the way to finally achieve market authorization. Advantages of NK cell therapies include the use of allogenic cell sources, off-the-shelf availability, and no risk of graft-versus-host disease (GvHD). Allogeneic NK cell therapies have reached the clinical stage as ex vivo expanded and differentiated non-engineered cells, as chimeric antigen receptor (CAR)-engineered or CD16-engineered products, or as combination therapies with antibodies, priming agents, and other drugs. This review summarizes the recent clinical status of allogeneic NK cell-based therapies for the treatment of hematological and solid tumors, discussing the main characteristics of the different cell sources used for NK product development, their use in cell manufacturing processes, the engineering methods and strategies adopted for genetically modified products, and the chosen approaches for combination therapies. A comparative analysis between NK-based non-engineered, engineered, and combination therapies is presented, examining the choices made by product developers regarding the NK cell source and the targeted tumor indications, for both solid and hematological cancers. Clinical trial outcomes are discussed and, when available, assessed in comparison with preclinical data. Regulatory challenges for product approval are reviewed, highlighting the lack of specificity of requirements and standardization between products. Additionally, the competitive landscape and business field is presented. This review offers a comprehensive overview of the effort driven by biotech and pharmaceutical companies and by academic centers to bring NK cell therapies to pivotal clinical trial stages and to market authorization.