bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual and reproductive health information needs; an inquiry from the lens of in-school adolescents in Ebonyi State, Southeast Nigeria
Authors: Agu Ozioma , Agu Ifunanya Clara , Eigbiremolen Godstime , Akamike Ifeyinwa , Okeke Chinyere , Mbachu Chinyere , Onwujekwe Obinna
Published: April 2024

Background

It is important to understand the sexual and reproductive health (SRH) needs of adolescents from the adolescents themselves to address their needs properly. Hence, this paper provides new knowledge on the information needs on SRH among adolescent boys and girls in selected secondary schools in Ebonyi state, southeast Nigeria.

Method

A comparative assessment was conducted among adolescent boys and girls in public secondary schools that received a specific school-based SRH intervention (group A) and those that did not receive the intervention (group B). These schools were spread across six urban and rural local government areas in Ebonyi state, southeast Nigeria. A structured interviewer-administered questionnaire was used to collect data from 514 adolescents aged 13 to 18 on their stated needs for SRH information and services. Categorical variables were compared using the Chi-square test, and predictors were determined using logistic regression analysis. The statistical significance was determined at p < 0.05.

Result

Majority of the adolescents (82% of intervention group and 92% of non-intervention group) identified puberty and pubertal changes as perceived SRH information need for adolescents (χ2 = 7.94; p-value = 0.01). Adolescents who received SRH intervention have 3.13 (p < 0.001) times the odds of perceiving the need for adolescents to be provided with SRH information than adolescents who did not receive SRH intervention. The odds of perceiving the need for adolescents to be provided with SRH information for adolescents who reside in urban communities are 0.31 (p < 0.001) times the odds for adolescents who resides in rural communities. That is, the perception odds are higher adolescents who reside in rural communities. Multivariate regression of specific SRH information showed the location of residence as a strong predictor of adolescents’ perceived need for information on ‘puberty and pubertal changes’ (OR = 0.30; p = 0.001), ‘safe sex and sexual relations’ (OR = 0.33; p < 0.001) and ‘prevention of pregnancy and use of contraceptives’ (OR = 0.28; p < 0.001). Adolescents in senior secondary school have 2.21 (p = 0.002) times the odds of perceiving the need for adolescents to be provided with specific SRH information than adolescents who are in junior secondary school.

Conclusion

Adolescents’ age, location of residence, and study group were found to be strong predictors of SRH information needs. This suggests the need for in-school adolescents to be provided with substantial and continuous SRH information for healthy living and making informed SRH choices. In developing SRH interventions that will achieve optimal effectiveness in the lives of adolescents in school, different demographic factors should be considered for context-specific and appropriate strategies.
Transient pulmonary and gastric bleeding after iopamidol administration in a patient with marginal zone lymphoma: a case report
Authors: Xu Weixian , Chen Miaozhen , Liu Songtao , Su Yi , Zhang Yunhai
Published: April 2024

Background

Iopamidol is a non-ionic, water-soluble iodine contrast agent that is considered safe for intravenous or intra-arterial administration and is widely used both in the general population and in patients undergoing oncological treatment. While adverse reactions to iopamidol have been documented, to date, no pulmonary and gastric hemorrhages induced by iopamidol have been reported in oncology patients. We report the first case of this complication.

Case presentation

We report the case of a 60-year-old woman with marginal zone lymphoma who was receiving antineoplastic therapy. As part of the investigation for the condition, she underwent chest enhancement CT with iopamidol. Shortly thereafter(within five minutes), she experienced hemoptysis and hematemesis. She was intubated and admitted to the intensive care unit. Pre- and post-contrast images demonstrated the course of the hemorrhage. Flexible bronchoscopy and gastroscopy on the following day showed no active bleeding, and the patient recovered completely after antiallergy treatment. We speculate that contrast-induced hypersensitivity was the most likely cause of the transient pulmonary and gastric bleeding.

Conclusion

Although rare, the complications of iopamidol, which may cause allergic reactions in the lungs and stomach, should be considered.
Unusual cause of muscle weakness, type II respiratory failure and pulmonary hypertension: a case report of ryanodine receptor type 1(RYR1)-related myopathy
Authors: Chen Yinong , Zhang Shuai , Lu Xin , Xie Wanmu , Wang Chen , Zhai Zhenguo
Published: April 2024

Background

Patients with congenital myopathies may experience respiratory involvement, resulting in restrictive ventilatory dysfunction and respiratory failure. Pulmonary hypertension (PH) associated with this condition has never been reported in congenital ryanodine receptor type 1(RYR1)-related myopathy.

Case presentation

A 47-year-old woman was admitted with progressively exacerbated chest tightness and difficulty in neck flexion. She was born prematurely at week 28. Her bilateral lower extremities were edematous and muscle strength was grade IV−. Arterial blood gas analysis revealed hypoventilation syndrome and type II respiratory failure, while lung function test showed restrictive ventilation dysfunction, which were both worse in the supine position. PH was confirmed by right heart catheterization (RHC), without evidence of left heart disease, congenital heart disease, or pulmonary artery obstruction. Polysomnography indicated nocturnal hypoventilation. The ultrasound revealed reduced mobility of bilateral diaphragm. The level of creatine kinase was mildly elevated. Magnetic resonance imaging showed myositis of bilateral thigh muscle. Muscle biopsy of the left biceps brachii suggested muscle malnutrition and congenital muscle disease. Gene testing revealed a missense mutation in the RYR1 gene (exon33 c.C4816T). Finally, she was diagnosed with RYR1-related myopathy and received long-term non-invasive ventilation (NIV) treatment. Her symptoms and cardiopulmonary function have been greatly improved after 10 months.

Conclusions

We report a case of RYR1-related myopathy exhibiting hypoventilation syndrome, type II respiratory failure and PH associated with restrictive ventilator dysfunction. Pulmonologists should keep congenital myopathies in mind in the differential diagnosis of type II respiratory failure, especially in patients with short stature and muscle weakness.
Long-term follow-up after the treatment of impacted canines in the maxilla causing severe root resorption of the lateral incisors: two case reports
Authors: LI Ning , YANG Liu , YANG Qian , WANG Hongning , XU Xiaolin , WANG Tiejun
Published: April 2024

Background

Root resorption of adjacent teeth due to impacted canines is common, and orthodontic treatment often leads to secondary resorption or even loss of adjacent roots. Clinical reports of long-term stability after treatment are rare.

Case presentation

This study reports two cases of maxillary impacted canines resulting in severe root resorption of the adjacent lateral incisors. Surgical exposure, orthodontic retraction, and alignment of the impacted canines were successful in both cases, and the resorbed lateral incisors were stable with no significant loosening and normal pulp vitality after treatment and at the 5- and 10-year follow-up appointments.

Conclusions

Light orthodontic force may be used to move adjacent teeth with root resorption due to tooth obstruction. The path and direction in which the teeth are moved must be specifically designed so that the adjacent roots are not resorbed and so long-term stability can be achieved.
Use of bone landmarks for assessing the safety of acupuncture on the posterior midline of the neck region
Authors: Tang Zhiliang , Liu Jiao , Li Jin , Ma Chunming
Published: April 2024

Objective

Many acupuncture acupoints are located on the posterior midline of the neck region. The needling depth for acupuncture is important for practitioners, and an unsafe needling depth increases the possibility of damage to the spinal cord and brainstem. Can the safety of acupuncture be assessed by examining bone structures? We focused on this aim to carry out this study.

Methods

The shortest distance from the posterior border of the foramen magnum to the line joining both upper ends of the posterior border of the mastoid process was measured on 29 skulls. Distances from the posterior border of the vertebral foramen to the tip of the spinous process and posterior tubercle of the atlas were measured and evaluated from 197 dry cervical vertebrae and 31 lateral cervical radiographs of patient subjects. The anatomic relationships of the vertebral canal with the external occipital protuberance, tip of the spinous process of the axis, tip of the posterior tubercle of the atlas, and upper end of the posterior border of the mastoid process were observed and evaluated via lateral cervical radiography.

Results

The shortest distance from the foramen magnum to the line between the mastoid processes was 4.65±1.75 mm, and the distance from the superior border of the vertebral foramen of the atlas to the posterior tubercle was less than the distance from the inferior border. The distance from the superior border of the vertebral canal to the tip of the spinous process in C2-C7 was greater than the distance from the inferior border. The mean lengths of the superior border of the C2 spinous process and the inferior border of the C7 spinous process were greater than 21 mm and 31 mm, respectively. The line from the upper end of the posterior border of the mastoid process to the tip of the C2 spinous process or 10 mm deep to the tip of the C2 spinous process was posterior to the vertebral canal.

Conclusions

On the posterior midline of the neck region between the tip of spinous process of axis and external occipital protuberance, if the needle reaches the depth of the line between the upper end of posterior border of mastoid process and the tip of the spinous process of the axis, approximately 10 mm along the spinous process of the axis, the needle is in the safe region. The mean length of the C2-C7 spinous process is suitable to accommodate the needling depth of the adjacent acupoint. Bone structures can be used to effectively assess the safety of acupuncture on the posterior midline of the neck region.
Molar root canal treatment performed by undergraduate dental students; an observational study of procedural errors and student perception
Authors: El-Ma’aita Ahmad M. , Mahasneh Sari A. , Hamandi Maryam A. , Al-Rabab’ah Mohammad A.
Published: April 2024

Background

Molar root canal treatment (RCT) is challenging and requires training and specific skills. Rotary instrumentation (RI) reduces the time needed for instrumentation but may increase the risk of certain procedural errors. The aims of this study were to evaluate the quality of molar RCTs provided by undergraduate students, to compare the prevalence of procedural errors following manual and RI, and to assess the students’ self-perceived confidence to perform molar RCT without supervision and their preference for either manual or RI.

Methods

Molar RCTs performed by the final year students were evaluated radiographically according to predefined criteria (Appendix 1). The procedural errors, treatment details, and the students’ self-perceived confidence to perform molar RCT and their preference for either manual or RI were recorded. Descriptive statistics were performed, and the Chi-squared test was used to detect any statistically significant differences.

Results

60.4% of RCTs were insufficient. RI resulted in more sufficient treatments compared with MI (49% vs. 30.3% respectively. X2: 7.39, p = 0.007), required fewer visits to complete (2.9 vs. 4.6 respectively. X2: 67.23, p < 0.001) and was the preferred technique by 93.1% of students. The most common procedural errors were underextension of the root canal obturation (48.4%), insufficient obturation (45.5%), and improper coronal seal (35.2%) without a significant difference between the two techniques. 26.4% of the participating students reported that they did not feel confident to perform molar RCT without supervision.

Conclusion

The quality of molar RCT provided by UG students was generally insufficient. RI partially improved the technical quality of RCT compared with MI. UG students need further endodontic training and experience before they can safely and confidently practise molar RCT.
Impact of COVID-19 pandemic on depression incidence and healthcare service use among patients with depression: an interrupted time-series analysis from a 9-year population-based study
Authors: Chan Vivien Kin Yi , Chai Yi , Chan Sandra Sau Man , Luo Hao , Jit Mark , Knapp Martin , Bishai David Makram , Ni Michael Yuxuan , Wong Ian Chi Kei , Li Xue
Published: April 2024

Background

Most studies on the impact of the COVID-19 pandemic on depression burden focused on the earlier pandemic phase specific to lockdowns, but the longer-term impact of the pandemic is less well-studied. In this population-based cohort study, we examined the short-term and long-term impacts of COVID-19 on depression incidence and healthcare service use among patients with depression.

Methods

Using the territory-wide electronic medical records in Hong Kong, we identified all patients aged ≥ 10 years with new diagnoses of depression from 2014 to 2022. We performed an interrupted time-series (ITS) analysis to examine changes in incidence of medically attended depression before and during the pandemic. We then divided all patients into nine cohorts based on year of depression incidence and studied their initial and ongoing service use patterns until the end of 2022. We applied generalized linear modeling to compare the rates of healthcare service use in the year of diagnosis between patients newly diagnosed before and during the pandemic. A separate ITS analysis explored the pandemic impact on the ongoing service use among prevalent patients with depression.

Results

We found an immediate increase in depression incidence (RR = 1.21, 95% CI: 1.10–1.33, p < 0.001) in the population after the pandemic began with non-significant slope change, suggesting a sustained effect until the end of 2022. Subgroup analysis showed that the increases in incidence were significant among adults and the older population, but not adolescents. Depression patients newly diagnosed during the pandemic used 11% fewer resources than the pre-pandemic patients in the first diagnosis year. Pre-existing depression patients also had an immediate decrease of 16% in overall all-cause service use since the pandemic, with a positive slope change indicating a gradual rebound over a 3-year period.

Conclusions

During the pandemic, service provision for depression was suboptimal in the face of increased demand generated by the increasing depression incidence during the COVID-19 pandemic. Our findings indicate the need to improve mental health resource planning preparedness for future public health crises.
A novel variant in NSUN2 causes intellectual disability in a Chinese family
Authors: Yang Qi , Zhang Qiang , Qin Zailong , Yi Shang , Luo Jingsi
Published: April 2024

NSUN2-intellectual disability syndrome, also known as intellectual disability type 5 (MRT5), is an autosomal recessive disorder that is characterized by intellectual disability (ID), postnatal growth retardation, dysmorphic facies, microcephaly, short stature, developmental delay, language impairment and other congenital abnormalities. The disease is caused by mutations in the NSUN2 gene, which encodes a tRNA cytosine methyltransferase that has an important role in spindle assembly during mitosis and chromosome segregation. In this study, we recruited a family that had two individuals with ID. Whole exome sequencing was performed to identify a homozygous frameshift variant (c.1171_1175delACCAT(p.Thr391fs*18*)) in NSUN2 (NM_017755.5) in the proband. The varint was confirmed as segregating in his affected brother and his parents by Sanger sequencing. The individuals that we described showed a similar dysmorphology profile to that associated with MRT5. To analyze the correlations between genotypes of NSUN2 and phenotypes of individuals with ID, we examined 17 variants and the associated phenotypes from 32 ID individuals in current and previous studies. We concluded that mutations in NSUN2 cause a wide range of phenotypic defects. Although some clinical manifestations were highly variable, the core phenotypes associated with NSUN2 mutations were dysmorphic facies, microcephaly, short stature, ID, growth restriction, language impairment, hypotonia and delayed puberty. Our study expands the genetic spectrum of NSUN2 mutations and helps to further define the genotype-phenotype correlations in MRT5.
Let it glow: genetically encoded fluorescent reporters in Plasmodium
Authors: Thiele Pia J. , Mela-Lopez Raquel , Blandin Stéphanie A. , Klug Dennis
Published: April 2024

The use of fluorescent proteins (FPs) in Plasmodium parasites has been key to understand the biology of this obligate intracellular protozoon. FPs like the green fluorescent protein (GFP) enabled to explore protein localization, promoter activity as well as dynamic processes like protein export and endocytosis. Furthermore, FP biosensors have provided detailed information on physiological parameters at the subcellular level, and fluorescent reporter lines greatly extended the malariology toolbox. Still, in order to achieve optimal results, it is crucial to know exactly the properties of the FP of choice and the genetic scenario in which it will be used. This review highlights advantages and disadvantages of available landing sites and promoters that have been successfully applied for the ectopic expression of FPs in Plasmodium berghei and Plasmodium falciparum. Furthermore, the properties of newly developed FPs beyond DsRed and EGFP, in the visualization of cells and cellular structures as well as in the sensing of small molecules are discussed.

Graphical Abstract
Exosomal miR-9-5p derived from iPSC-MSCs ameliorates doxorubicin-induced cardiomyopathy by inhibiting cardiomyocyte senescence
Authors: Zheng Huifeng , Liang Xiaoting , Liu Baojuan , Huang Xinran , Shen Ying , Lin Fang , Chen Jiaqi , Gao Xiaoyan , He Haiwei , Li Weifeng , Hu Bei , Li Xin , Zhang Yuelin
Published: April 2024

Doxorubicin (DOX) is a chemotherapeutic agent widely used for tumor treatment. Nonetheless its clinical application is heavily limited by its cardiotoxicity. There is accumulated evidence that transplantation of mesenchymal stem cell-derived exosomes (MSC-EXOs) can protect against Dox-induced cardiomyopathy (DIC). This study aimed to examine the cardioprotective effects of EXOs isolated from human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) against DIC and explore the potential mechanisms. EXOs were isolated from the cultural supernatant of human BM-MSCs (BM-MSC-EXOs) and iPSC-MSCs (iPSC-MSC-EXOs) by ultracentrifugation. A mouse model of DIC was induced by intraperitoneal injection of Dox followed by tail vein injection of PBS, BM-MSC-EXOs, or iPSC-MSC-EXOs. Cardiac function, cardiomyocyte senescence and mitochondrial dynamics in each group were assessed. In vitro, neonatal mouse cardiomyocytes (NMCMs) were subjected to Dox and treated with BM-MSC-EXOs or iPSC-MSC-EXOs. The mitochondrial morphology and cellular senescence of NMCMs were examined by Mitotracker staining and senescence-associated-β-galactosidase assay, respectively. Compared with BM-MSC-EXOs, mice treated with iPSC-MSC-EXOs displayed improved cardiac function and decreased cardiomyocyte mitochondrial fragmentation and senescence. In vitro, iPSC-MSC-EXOs were superior to BM-MSC-EXOs in attenuation of cardiomyocyte mitochondrial fragmentation and senescence caused by DOX. MicroRNA sequencing revealed a higher level of miR-9-5p in iPSC-MSC-EXOs than BM-MSC-EXOs. Mechanistically, iPSC-MSC-EXOs transported miR-9-5p into DOX-treated cardiomyocytes, thereby suppressing cardiomyocyte mitochondrial fragmentation and senescence via regulation of the VPO1/ERK signal pathway. These protective effects and cardioprotection against DIC were largely reversed by knockdown of miR-9-5p in iPSC-MSC-EXOs. Our results showed that miR-9-5p transferred by iPSC-MSC-EXOs protected against DIC by alleviating cardiomyocyte senescence via inhibition of the VPO1/ERK pathway. This study offers new insight into the application of iPSC-MSC-EXOs as a novel therapeutic strategy for DIC treatment.

Graphical Abstract
Pregnancy and acromegaly: clinical outcomes of retrospectively analysed data from the German acromegaly registry
Authors: Tönjes Anke , Würfel Marleen , Quinkler Marcus , Knappe Ulrich J. , Honegger Jürgen , Krause-Joppig Nina , Bacher Konrad , Deutschbein Timo , Störmann Sylvère , Schopohl Jochen , Meyhöfer Sebastian M. ,   the participants of the German Acromegaly Registry, Meyer Almuth , Gruber Matthias , Wortmann Stefanie , Klasen Christine , Karges Wolfram , Demtröder Frank , Frenzke Hanna , Laubner Katharina , Finke Reinhard
Published: April 2024

Context

Acromegaly is a rare disease caused by excessive growth hormone (GH) secretion, mostly induced by pituitary adenomas. The care of pregnant women with acromegaly is challenging, in part due to existing clinical data being limited and not entirely consistent with regard to potential risks for mother and child.

Objective

To retrospectively examine data on pregnancy and maternal as well as neonatal outcomes in patients with acromegaly.

Design & methods

Retrospective data analysis from 47 pregnancies of 31 women treated in centers of the German Acromegaly Registry.

Results

87.1% of the studied women underwent transsphenoidal surgery before pregnancy. In 51.1% a combination of dopamine agonists and somatostatin analogs were used before pregnancy. Three women did not receive any therapy for acromegaly. During pregnancy only 6.4% received either somatostatin analogs or dopamine agonists. In total, 70.2% of all documented pregnancies emerged spontaneously. Gestational diabetes was diagnosed in 10.6% and gravid hypertension in 6.4%. Overall, no preterm birth was detected. Indeed, 87% of acromegalic women experienced a delivery without complications.

Conclusion

Pregnancies in women with acromegaly are possible and the course of pregnancy is in general safe for mother and child both with and without specific treatment for acromegaly. The prevalence of concomitant metabolic diseases such as gestational diabetes is comparable to the prevalence in healthy pregnant women. Nevertheless, larger studies with more data in pregnant patients with acromegaly are needed to provide safe and effective care for pregnant women with this condition.
One-hole split endoscope versus unilateral biportal endoscopy for lumbar spinal stenosis: a retrospective propensity score study
Authors: Li Tusheng , Jiang Qiang , Zhong Wei , Zhu Tengyue , Lu Zhengcao , Ding Yu
Published: April 2024

Background

The one-hole split endoscopy (OSE) was first proposed and clinically applied in China in 2019. The aim of this study was to compare the clinical efficacy of one-hole split endoscopy (OSE) and unilateral biportal endoscopy (UBE) for treating lumbar spinal stenosis (LSS).

Methods

One hundred sixty patients with LSS who met the inclusion from November 2020 to August 2022 were analyzed and divided into OSE and UBE groups. The propensity score matching (PSM) method was used to adjust the imbalanced confounding variables between the two groups. After matching, surgical outcomes were recorded, and clinical data, including functional scores and imaging findings, were compared. Functional scores included the visual analog scale of leg pain (VAS-LP) and back pain (VAS-BP), the Japanese Orthopedic Association score (JOA), and the Oswestry Disability Index (ODI). Imaging data included dural sac cross-sectional area (DCSA), lumbar range of motion (ROM), and sagittal translation (ST).

Results

After PSM, 104 LSS patients were included in the study, and all covariates were well-balanced between the two groups. Among the matched patients, the OSE showed advantages over the UBE regarding operative time (62.42 ± 4.86 vs. 68.96 ± 4.56) and incision length (2.30 ± 0.14 vs. 2.70 ± 0.15) (P < 0.001). However, differences between the two groups in intraoperative blood loss, hospital length of stay, and complication rates were not statistically significant (P > 0.05). There was no statistically significant difference regarding VAS-BP, VAS-LP, JOA, and ODI between the two groups (P > 0.05). However, all clinical and functional scores significantly improved postoperatively (P < 0.05). Postoperative DCSA of both groups was significantly found to be improved (P < 0.05), ROM and ST remained within the normal range, and no cases of lumbar instability were recorded. According to the modified MacNab criteria, the excellent and good rates in the OSE and UBE groups were 94.23% and 90.38%, respectively, with no statistically significant difference (P = 0.713).

Conclusion

OSE is an alternative technique to UBE for the treatment of LSS, with similar satisfactory clinical outcomes, shorter operative time, and smaller incision length. Further studies are needed for long-term efficacy.
Access to care in Afghanistan after august 2021: a cross-sectional study exploring Afghans’ perspectives in 10 provinces
Authors: Valente Martina , Lamberti-Castronuovo Alessandro , Bocchini Francesca , Shafiq Yasir , Trentin Monica , Paschetto Michela , Bahdori Ghulam Ali , Khadem Jan Agha , Nadeem Mirza Sayed , Patmal Mohammand Hanif , Alizai Mohammad Tawoos , Barone-Adesi Francesco , Miccio Rossella , Ragazzoni Luca
Published: April 2024

Background

The Taliban takeover in August 2021 ended a decades-long conflict in Afghanistan. Yet, along with improved security, there have been collateral changes, such as the exacerbation of the economic crisis and brain drain. Although these changes have altered the lives of Afghans in many ways, it is unclear whether they have affected access to care. This study aimed to analyse Afghans’ access to care and how this access has changed after August 2021.

Methods

The study relied on the collaboration with the non-governmental organisation EMERGENCY, running a network of three hospitals and 41 First Aid Posts in 10 Afghan provinces. A 67-item questionnaire about access to care changes after August 2021 was developed and disseminated at EMERGENCY facilities. Ordinal logistic regression was used to evaluate whether access to care changes were associated with participants’ characteristics.

Results

In total, 1807 valid responses were returned. Most respondents (54.34%) reported improved security when visiting healthcare facilities, while the ability to reach facilities has remained stable for the majority of them (50.28%). Care is less affordable for the majority of respondents (45.82%). Female respondents, those who are unmarried and not engaged, and patients in the Panjshir province were less likely to perceive improvements in access to care.

Conclusions

Findings outline which dimensions of access to care need resource allocation. The inability to pay for care is the most relevant barrier to access care after August 2021 and must therefore be prioritised. Women and people from the Panjshir province may require ad hoc interventions to improve their access to care.
Clustering of HR + /HER2− breast cancer in an Asian cohort is driven by immune phenotypes
Authors: Pan Jia-Wern , Ragu Mohana , Chan Wei-Qin , Hasan Siti Norhidayu , Islam Tania , Teoh Li-Ying , Jamaris Suniza , See Mee-Hoong , Yip Cheng-Har , Rajadurai Pathmanathan , Looi Lai-Meng , Taib Nur Aishah Mohd , Rueda Oscar M. , Caldas Carlos , Chin Suet-Feung , Lim Joanna , Teo Soo-Hwang
Published: April 2024

Breast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2− breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent. This suggests that the activation of the immune system may play a more important role in Asian HR + /HER2− breast cancer than has been previously recognized. Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR + /HER2− samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.
Ki-67 is necessary during DNA replication for fork protection and genome stability
Authors: Stamatiou Konstantinos , Huguet Florentin , Serapinas Lukas V. , Spanos Christos , Rappsilber Juri , Vagnarelli Paola
Published: April 2024

Background

The proliferation antigen Ki-67 has been widely used in clinical settings for cancer staging for many years, but investigations on its biological functions have lagged. Recently, Ki-67 has been shown to regulate both the composition of the chromosome periphery and chromosome behaviour in mitosis as well as to play a role in heterochromatin organisation and gene transcription. However, how the different roles for Ki-67 across the cell cycle are regulated and coordinated remain poorly understood. The progress towards understanding Ki-67 function have been limited by the tools available to deplete the protein, coupled to its abundance and fluctuation during the cell cycle.

Results

Here, we use a doxycycline-inducible E3 ligase together with an auxin-inducible degron tag to achieve a rapid, acute and homogeneous degradation of Ki-67 in HCT116 cells. This system, coupled with APEX2 proteomics and phospho-proteomics approaches, allows us to show that Ki-67 plays a role during DNA replication. In its absence, DNA replication is severely delayed, the replication machinery is unloaded, causing DNA damage that is not sensed by the canonical pathways and dependent on HUWE1 ligase. This leads to defects in replication and sister chromatids cohesion, but it also triggers an interferon response mediated by the cGAS/STING pathway in all the cell lines tested.

Conclusions

We unveil a new function of Ki-67 in DNA replication and genome maintenance that is independent of its previously known role in mitosis and gene regulation.
Efficacy of Wearable low-intensity pulsed Ultrasound treatment in the Movement disorder in Parkinson’s disease (the SWUMP trial): protocol for a single-site, double-blind, randomized controlled trial
Authors: Zhong Chuanyu , Guo Ning , Hu Canfang , Ni Ruilong , Zhang Xiaojie , Meng Zheying , Liu Taotao , Ding Siqi , Ding Wanhai , Zhao Yuwu , Cao Li , Zheng Yuanyi
Published: April 2024

Background

Parkinson’s disease (PD) is a progressive, neurodegenerative illness marked by the loss of dopaminergic neurons, causing motor symptoms. Oral levodopa replacement therapy remains the gold standard in the treatment of PD. It is, nevertheless, a symptomatic treatment. There is currently no effective treatment for PD. Therefore, new therapies for PD are highly desirable. Low-intensity pulsed ultrasound (LIPUS) has been shown to improve behavioral functions in PD animal models. It is a new type of neuromodulation approach that combines noninvasiveness with high spatial precision. The purpose of this study is to establish a new clinical protocol for LIPUS in the treatment of movement disorders in patients with PD.

Methods

This protocol is a single-site, prospective, double-blind, randomized controlled trial (RCT). Forty-eight participants with clinically confirmed PD will be randomly allocated to one of two groups: LIPUS group or sham group. All of the participants continue to use pharmacological therapy as a fundamental treatment. The primary outcome is the difference between groups from baseline to 4 months in the change in the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score (part III). The secondary outcomes include the rating scales such as the Mini-Mental State Examination (MMSE), and other three rating scales, and medical examinations including high-density electroencephalography (hdEEG) and functional magnetic resonance imaging (fMRI). The primary safety outcome will be assessed at 4 months, and adverse events will be recorded.

Discussion

This study represents the clinical investigation into the efficacy of therapeutic LIPUS in the treatment of PD for the first time. If LIPUS is determined to be effective, it could offer a practical and innovative means of expanding the accessibility of ultrasound therapy by using a wearable LIPUS device within a home setting.

Trial registration

Chinese Clinical Trial Registry ChiCTR2100052093. Registered on 17 October 2021.
Poly (aniline-co-aniline-2,5-disulfonic acid) / L-ascorbic acid / Ag@SiO2 / polysafranin nanocomposite: synthesis, characterization and anomalous electrical behaviour
Authors: Hassan Hammed H. A. M. , Fattah Marwa Abdel , Maged Fatma Abdel
Published: April 2024

We report the synthesis of sulfonated copolyaniline/polysafranin/L-ascorbic acid/Ag@SiO2 fine powdered nanocomposites and investigate the influence of incorporating the dye on their conductivity. The composite was characterized via IR, UV, cyclic voltammetry (CV), electric, dielectric, SEM, TEM, TGA and DSC measurements. Microscopy images revealed intensified spherical particles that were dispersed across the entire surface, and the SiO2/Ag particles were distributed on the surface. The XRD results exhibited peaks at many 2q values, and their interatomic spacing (d) and crystallite (grain) sizes were calculated. The thermal degradation curves exhibited an interesting model of stability. The cyclic voltammogram exhibited redox peaks identical to those of the reported analogues. The d.c. conductivity of the oligomer varied from 0.06 − 0.016 (s/cm), and that of the composite varied from 0.008 to 0.016 (s/cm). The material changed from a semiconductor to a metallic material. The observed conductivity is mainly attributed to self-doping between the sulfonate groups and the charged nitrogen atoms in the polymer chains. The frequency dependence of the permittivity, ε′, showed a marked effect on the frequency window under consideration. The permittivity, ε′, is independent of the increase in the frequency of the oligomer and the composite. This behavior supports the non-Debye dependency by confirming the occurrence of electrode polarization and space charge effects. In conclusion, the incorporation of safranin dye with a thermally stable, highly sulfonated polyaniline derivative/Ag@SO2 nanocomposite achieved improved conductivity after heating. The d.c. conductivities are comparable to those of many commercial inorganic or organic composites, and because of their attractive electrical properties, we suggest that these materials are promising for electronic field applications.
Colorimetric sensor array for versatile detection and discrimination of model analytes with environmental relevance
Authors: Adampourezare Mina , Nikzad Behzad , Sajedi-Amin Sanaz , Rahimpour Elaheh
Published: April 2024

In the current work, a rapid, simple, low-cost, and sensitive smartphone-based colorimetric sensor array coupled with pattern-recognition methods was proposed for the determination and differentiation of some organic and inorganic bases (i.e., OH−, CO32−, PO43−, NH3, ClO−, diethanolamine, triethanolamine) as model compounds. The sensing system has been designed based on color-sensitive dyes (Fuchsine, Giemsa, Thionine, and CoCl2) which were used as sensor elements. The color changes of a sensor array were observed by the naked eye. The color patterns were recorded using digital imaging in a three-dimensional (red, green, and blue) space and quantitatively analyzed with color calibration techniques. Distinctive colorimetric patterns for target bases via linear discriminant analysis (LDA) and hierarchical clustering analysis (HCA) were observed. The results indicated that the analytes related to each class (at the different concentration levels in the range of 0.001–1.0 mol L−1) were clustered together in the canonical discriminant plot and HCA dendrogram with high sensitivity and an overall precision of 85%. Furthermore, the first function factor of LDA correlated with the concentration of each target analyte in a correlation coefficient (R2) range of 0.864–0.996. These described procedures based on the colorimetric sensor array technique could be a promising candidate for practical applications in package technology and facile detection of pollutants.
Small GTPase Rab7 is involved in stress adaptation to carbon starvation to ensure the induced cellulase biosynthesis in Trichoderma reesei
Authors: Liu Lin , Wang Zhixing , Fang Yu , Yang Renfei , Pu Yi , Meng Xiangfeng , Liu Weifeng
Published: April 2024

Background

The saprophytic filamentous fungus Trichoderma reesei represents one of the most prolific cellulase producers. The bulk production of lignocellulolytic enzymes by T. reesei not only relies on the efficient transcription of cellulase genes but also their efficient secretion after being translated. However, little attention has been paid to the functional roles of the involved secretory pathway in the high-level production of cellulases in T. reesei. Rab GTPases are key regulators in coordinating various vesicle trafficking associated with the eukaryotic secretory pathway. Specifically, Rab7 is a representative GTPase regulating the transition of the early endosome to the late endosome followed by its fusion to the vacuole as well as homotypic vacuole fusion. Although crosstalk between the endosomal/vacuolar pathway and the secretion pathway has been reported, the functional role of Rab7 in cellulase production in T. reesei remains unknown.

Results

A TrRab7 was identified and characterized in T. reesei. TrRab7 was shown to play important roles in T. reesei vegetative growth and vacuole morphology. Whereas knock-down of Trrab7 significantly compromised the induced production of T. reesei cellulases, overexpression of the key transcriptional activator, Xyr1, restored the production of cellulases in the Trrab7 knock-down strain (Ptcu-rab7KD) on glucose, indicating that the observed defective cellulase biosynthesis results from the compromised cellulase gene transcription. Down-regulation of Trrab7 was also found to make T. reesei more sensitive to various stresses including carbon starvation. Interestingly, overexpression of Snf1, a serine/threonine protein kinase known as an energetic sensor, partially restored the cellulase production of Ptcu-rab7KD on Avicel, implicating that TrRab7 is involved in an energetic adaptation to carbon starvation which contributes to the successful cellulase gene expression when T. reesei is transferred from glucose to cellulose.

Conclusions

TrRab7 was shown to play important roles in T. reesei development and a stress response to carbon starvation resulting from nutrient shift. This adaptation may allow T. reesei to successfully initiate the inducing process leading to efficient cellulase production. The present study provides useful insights into the functional involvement of the endosomal/vacuolar pathway in T. reesei development and hydrolytic enzyme production.
Meal support intervention for eating disorders: a mixed-methods systematic review
Authors: Ellis Aleshia , Gillespie Kerri , McCosker Laura , Hudson Carly , Diamond Gideon , Machingura Tawanda , Branjerdporn Grace , Woerwag-Mehta Sabine
Published: April 2024

Objective

Mealtimes are a period of heightened distress for individuals with eating disorders. Patients frequently display maladaptive coping strategies, such as hiding food and using distraction techniques to avoid eating. The aim of this systematic review is to evaluate the evidence for meal support interventions as a first-line intervention for eating disorders.

Method

Six databases were systematically searched in January 2024. Papers including patients with an eating disorder, and meal support or meal supervision, were examined. Quality appraisal was conducted.

Results

Ten studies met inclusion criteria. Meal support was conducted individually and in group settings. Two studies examined the practical or interpersonal processes of meal support. Carers and trained clinicians implemented meal support. Individuals across the lifespan were examined. Settings included inpatient units, community clinics, and the home. Studies were heterogeneously evaluated with retrospective chart audits, pre- and post- cohort studies, semi-structured interviews, video analysis, and surveys.

Discussion

Meal support intervention is potentially suitable and beneficial for patients of various age groups and eating disorder diagnoses. Due to the lack of consistent approaches, it is apparent there is no standardised framework and manualised approach. This highlights the need for the development of a co-designed approach, adequate training, and rigorous evaluation.
Improved survival on super high-flux albumin-leaking hemodialysis and online hemodiafiltration with high albumin leakage in patients with mild hypoalbuminemia: evidence and a hypothesis
Authors: Okada Kazuyoshi , Tashiro Manabu , Michiwaki Hiroyuki , Inoue Tomoko , Shima Hisato , Minakuchi Jun
Published: April 2024

It has been reported that survival on mild hypoalbuminemia due to high albumin leakage did not worsen in patients on hemodialysis (HD) or online hemodiafiltration (OHDF) even though the level of serum albumin is a classic nutrition marker associated with mortality. Survival was also equivalent on HD and OHDF for patients with similar levels of albumin leakage and serum albumin. Furthermore, survival on HD using a super high-flux (SHF) albumin-leaking membrane was better than that on HD using a SHF membrane, and survival on SHF albumin-leaking HD with high albumin leakage was better than that on OHDF with low albumin leakage. The following hypothesis regarding crosstalk between α1-microglobulin (α1MG) and albumin is proposed that can explain the mechanism by which the level of serum human mercaptoalbumin (HMA) increases postdialysis and decreases predialysis. At initiation of and during dialysis, the production of free α1MG in the liver increases by upregulation of the α1MG-bikunin precursor gene. The free α1MG rapidly reacts with some substances that are reversibly bound to human nonmercaptoalbumin (HNA)-1, resulting in the conversion to HMA and free α1MG with reduced activity (i.e., free α1MG with reduced or no antioxidant capacity) during dialysis and in the increased serum HMA level postdialysis. In addition, it is possible that both hypoalbuminemia and the conversion of HNA-1 to HMA increase the free form of indoxyl sulfate, which is removed by diffusion. The antioxidant capacity in serum after dialysis is mainly due to the very large amount of HMA, resulting in the conversion to HNA and the decreased serum HMA level before dialysis. However, the very small amount of free α1MG produced in the liver has strong antioxidant activity after dialysis.
A review of animal models utilized in preclinical studies of approved gene therapy products: trends and insights
Authors: Soufizadeh Parham , Mansouri Vahid , Ahmadbeigi Naser
Published: April 2024

Scientific progress heavily relies on rigorous research, adherence to scientific standards, and transparent reporting. Animal models play a crucial role in advancing biomedical research, especially in the field of gene therapy. Animal models are vital tools in preclinical research, allowing scientists to predict outcomes and understand complex biological processes. The selection of appropriate animal models is critical, considering factors such as physiological and pathophysiological similarities, availability, and ethical considerations. Animal models continue to be indispensable tools in preclinical gene therapy research. Advancements in genetic engineering and model selection have improved the fidelity and relevance of these models. As gene therapy research progresses, careful consideration of animal models and transparent reporting will contribute to the development of effective therapies for various genetic disorders and diseases. This comprehensive review explores the use of animal models in preclinical gene therapy studies for approved products up to September 2023. The study encompasses 47 approved gene therapy products, with a focus on preclinical trials. This comprehensive analysis serves as a valuable reference for researchers in the gene therapy field, aiding in the selection of suitable animal models for their preclinical investigations.
Relationship of thymic area with clinical-epidemiological variables and values of T-lymphocyte subpopulations in peripheral blood of children with recurrent infections
Authors: Sotomayor Lugo Francisco , Zúñiga Rosales Yaíma , Pérez Martín Oliver , Hernández Reyes Evelyn , Antiguas Valdés Evelyn M. , Fundora Hernández Hermes , Rodríguez Guitiérrez Katia , Matas González Yaima , Hernández Imilla Casado , Villegas Valverde Carlos Agustín , Torres Rives Bárbara , Tam Rey Lázara Minerva , González Díaz Ihosvany , Hernández Rego Yaquima , Pita Ana María Simón , Macías Abraham Consuelo , Marcheco Teruel Beatriz
Published: April 2024

Background

Recurrent infections in childhood are the main cause of remission to the immunology service. T lymphocytes generated in the thymus are essential for fighting infection, making the thymus area an important predictor of the immune system’s competence. This study aimed to identify the possible relationship of the thymic area with clinical-epidemiological variables and values of subpopulations of T lymphocytes in the peripheral blood of children with recurrent infections.

Methods

We conducted applied research using a transversal analytical design at the National Medical Genetics Center (Havana, Cuba), from January to August 2022. The study covered 73 children of which we analyzed clinical-epidemiological variables and the size of the thymus through ultrasound. Furthermore, we determined the relative and absolute values of the subpopulations of T cells using flow cytometry.

Results

Of the children studied, 65.8% had thymic hypoplasia. The children who breastfed for less than 6 months showed four times the risk of developing moderate-severe thymus hypoplasia (OR = 3.90, 95% CI: 1.21–12.61). A direct relationship was found between the area of the thymus and the child’s size (r = 0.238, p = 0.043) and weight (r = 0.233, p = 0.047). The relative values of CD3+ T lymphocytes decreased in the cases of mild hypoplasia (p = 0.018) and moderate-severe hypoplasia (p = 0.049). The thymus area was associated with the absolute cell count of CD8+ effector memory T cells (rs = −0.263, p = 0.024) and of the central memory T cells (r = −0.283, p = 0.015).

Conclusions

Breastfeeding for less than 6 months, as well as the weight and size of the child, are related to their thymus area. The subpopulation values of T lymphocytes detected suggest that patients with thymic hypoplasia develop a contraction of CD3+ T cells, which can make them more vulnerable to infectious processes. This finding was combined with an expansion of the memory compartments of the subpopulations of CD8+ T cells, suggesting a greater susceptibility to intracellular viral and bacterial infections in these cases.