bluuebunny/crossref_metadata_2025 huggingface dataset:
Wee1 promotes cell proliferation and imatinib resistance in chronic myeloid leukemia via regulating DNA damage repair dependent on ATM-γH2AX-MDC1
Authors: Zeng Fanting , Peng Yuhang , Qin Yuefeng , Wang Jianming , Jiang Guoyun , Feng Wenli , Yuan Ying
Published: December 2022

Background

The treatment of chronic myeloid leukemia (CML) is facing the dilemma of tyrosine kinase inhibitors (TKIs) resistance and disease recurrence. The dysfunctional DNA damage repair mechanism plays an essential role not only in the initiation and progression of hematological malignancies but also links to the development of TKI resistance. Deciphering the abnormally regulated DNA damage repair and proteins involved brings new insights into the therapy of leukemias. As a G2/M phase checkpoint kinase and a DNA damage repair checkpoint kinase engaged in the DNA damage response (DDR), along with an oncogenic driver present in various cancers, the particular involvement of Wee1 in DNA damage is far from clear. Deciphering its function and targeting it via modulating DNA repair pathways is important for improving our understanding of cancer treatment.

Methods

Wee1 expression was assessed in cell lines using RT-qPCR and western blot, and Wee1 knockdown efficacy was validated using RT-qPCR, western blot, and immunofluorescence. Wee1 function was investigated by CCK-8, colony formation, and flow cytometry assay in vitro. Wee1 role in DNA repair and its interactions with other proteins were then studied using western blot, immunofluorescence, and double plasmid-repair studies. Finally, the CCK-8 and flow cytometry assay was utilized to investigate Wee1 and imatinib’s synergistic effect, and a CML mouse model was constructed to study Wee1’s role in carcinogenesis in vivo.

Results

Wee1 was reported to respond quickly to DDR in an ATM-γH2AX-MDC1-dependent way upon DNA double-strand breaks (DSBs) occurrence, and it regulated homologous recombination by stimulating the recruitment of critical proteins RAD51/BRCA1 upon DSB sites. Wee1 was also revealed to be abnormally upregulated in CML cells. Further suppression of Wee1 not only causes cell cycle arrest and inhibits the proliferation of cancer cells but also enhances CML cell sensitivity to Imatinib in vitro and in vivo, possibly through an excessive accumulation of overall DSBs.

Conclusion

Wee1 is extensively involved in the DRR signaling and DSB repair pathway. Inhibiting abnormally elevated Wee1 benefits CML therapy in both IM-resistant and IM-sensitive cells. Our data demonstrated that Wee1 participated in promoting cell proliferation and imatinib resistance in chronic myeloid leukemia via regulating DNA damage repair dependent on ATM-γH2AX-MDC1. In the fight against CML, Wee1’s dysregulation in the DNA damage repair mechanism of CML pathogenesis makes it a viable therapeutic target in clinical applications.
Cellular senescence in cancer: clinical detection and prognostic implications
Authors: Domen Andreas , Deben Christophe , Verswyvel Jasper , Flieswasser Tal , Prenen Hans , Peeters Marc , Lardon Filip , Wouters An
Published: December 2022

Cellular senescence is a state of stable cell-cycle arrest with secretory features in response to cellular stress. Historically, it has been considered as an endogenous evolutionary homeostatic mechanism to eliminate damaged cells, including damaged cells which are at risk of malignant transformation, thereby protecting against cancer. However, accumulation of senescent cells can cause long-term detrimental effects, mainly through the senescence-associated secretory phenotype, and paradoxically contribute to age-related diseases including cancer. Besides its role as tumor suppressor, cellular senescence is increasingly being recognized as an in vivo response in cancer patients to various anticancer therapies. Its role in cancer is ambiguous and even controversial, and senescence has recently been promoted as an emerging hallmark of cancer because of its hallmark-promoting capabilities. In addition, the prognostic implications of cellular senescence have been underappreciated due to the challenging detection and sparseinand ex vivo evidence of cellular senescence in cancer patients, which is only now catching up. In this review, we highlight the approaches and current challenges ofinand ex vivo detection of cellular senescence in cancer patients, and we discuss the prognostic implications of cellular senescence based oninand ex vivo evidence in cancer patients.
Efficacy of hearing aid treatment on sound perception and residual hearing preservation in patients with tinnitus and coexisting hearing loss: study protocol for a randomized controlled trial
Authors: Li Peifan , Tang Dongmei , Wu Yongzhen , Yin Yanbo , Sun Shan
Published: December 2022

Background

Chronic subjective tinnitus poses significant challenges in clinical practice, and it is usually associated with hearing impairment, particularly with high-frequency sensorineural hearing loss (SNHL). Patients suffering from tinnitus with SNHL experience one of the most severe sensory disabilities, and this has devastating effects on their quality of life. Nowadays, mild to moderate SNHL can be managed with a properly fitted hearing aid (HA) that provides sound amplification, and several studies suggest that HAs may also benefit those with tinnitus. However, inadequate attention has been paid by medical personnel to the impact of HA use in residual hearing protection for patients with tinnitus and coexisting SNHL, and existing evidence is still at a preliminary stage. This study aims to identify and evaluate the efficacy of the use of HAs in both sound perception and residual hearing preservation among patients with tinnitus and coexisting SNHL.

Methods and design

The present study is a prospective, single-center, outcome assessor and data analyst-blinded, randomized, controlled trial. Eligible participants will be recruited and randomly allocated into the HA intervention group and the waiting list control group at a ratio of 1:1. The primary outcome is to evaluate the severity of tinnitus using the Tinnitus Handicap Inventory as a continuous variable at 6 months from randomization. Secondary outcome measures include changes in hearing status and mental states. The trial will last 6 months, with follow-up visits at 3 months and 6 months.

Discussion

This will be the first randomized, controlled trial to identify and evaluate HAs’ efficacy on residual hearing preservation among tinnitus patients with coexisting high-frequency SNHL in China. We are aiming for novelty and generalizability, and strengths of this study are that it will examine the effectiveness of HA in patients with tinnitus and hearing impairment and will further explore the residual hearing protection provided by HA treatment in the tinnitus group.

Trial registration

ClinicalTrials.gov NCT05343026. Registered on April 25, 2022
Improved joint and patient-reported health assessments with pegloticase plus methotrexate co-therapy in patients with uncontrolled gout: 12-month exploratory outcomes of the MIRROR open-label trial
Authors: Botson John K. , Obermeyer Katie , LaMoreaux Brian , Zhao Lin , Weinblatt Michael E. , Peterson Jeff
Published: December 2022

Background

Uncontrolled/refractory gout patients are recalcitrant/intolerant to oral urate-lowering therapies (ULTs), experiencing frequent gout flares, functionally limiting tophi, and low quality of life. Pegloticase lowers urate, but anti-pegloticase antibodies limit urate-lowering efficacy and increase infusion reaction (IR) risk. Immunomodulator + pegloticase co-administration may improve treatment response rates, with 79% of MIRROR open-label trial (MIRROR-OL, pegloticase + oral methotrexate) participants meeting 6-month response criteria. Exploratory outcomes from MIRROR-OL are described here.

Methods

Adults with uncontrolled gout (serum urate [SU] ≥ 6 mg/dL and ULT-intolerance/recalcitrance or functionally limiting tophi) were included. Oral methotrexate (15 mg/week) was administered 4 weeks before and during pegloticase treatment (biweekly 8 mg infusion, ≤ 52 weeks). Exploratory outcomes included change from baseline (CFB) in number of affected joints, Health Assessment Questionnaires (HAQs), and Gout Global Assessments.

Results

Fourteen patients received ≥ 1 pegloticase infusion, with 13 included in 52-week analyses (1 enrolled before treatment-extension amendment, exited at 24 weeks). Three patients prematurely exited due to SU rise; 10 completed 52-week evaluations (8 completed 52 weeks of co-therapy, 2 completed 24 weeks [met treatment goals]). At 52 weeks, SU averaged 1.1 ± 2.5 mg/dL, with improvements in HAQ pain and health (CFB: − 33.6 and − 0.7, respectively), Patient and Physician Global Assessments (CFB: − 4.6 and − 5.7, respectively), and joint involvement (CFB: − 5.6, − 8.4, − 6.0 tender, swollen, tophi-affected joints, respectively). Two patients underwent dual-energy computed tomography, showing concomitant monosodium urate volume reductions. All patients had ≥ 1 AE, with 92.9% experiencing acute flare. One mild IR (“cough”) occurred and no new safety signals were identified.

Conclusion

Pegloticase + methotrexate co-therapy resulted in sustained SU-lowering with meaningful improvements in clinical measures, urate burden, and patient-reported outcomes.

Trial registration

ClinicalTrials.gov (NCT03635957)
Recent applications of machine learning and deep learning models in the prediction, diagnosis, and management of diabetes: a comprehensive review
Authors: Afsaneh Elaheh , Sharifdini Amin , Ghazzaghi Hadi , Ghobadi Mohadeseh Zarei
Published: December 2022

Diabetes as a metabolic illness can be characterized by increased amounts of blood glucose. This abnormal increase can lead to critical detriment to the other organs such as the kidneys, eyes, heart, nerves, and blood vessels. Therefore, its prediction, prognosis, and management are essential to prevent harmful effects and also recommend more useful treatments. For these goals, machine learning algorithms have found considerable attention and have been developed successfully. This review surveys the recently proposed machine learning (ML) and deep learning (DL) models for the objectives mentioned earlier. The reported results disclose that the ML and DL algorithms are promising approaches for controlling blood glucose and diabetes. However, they should be improved and employed in large datasets to affirm their applicability.
Prenatal diagnosis of distal 13q deletion syndrome in a fetus with esophageal atresia: a case report and review of the literature
Authors: Kotani Tomomi , Tsuda Hiroyuki , Ito Yumiko , Nakamura Noriyuki , Ushida Takafumi , Imai Kenji , Iitani Yukako , Fuma Kazuya , Muramatsu Yukako , Hayakawa Masahiro , Kajiyama Hiroaki
Published: December 2022

Background

Chromosome 13q deletion syndrome shows variable clinical features related to the different potential breakpoints in chromosome 13q. The severely malformed phenotype is known to be associated with the deletion of a critical region in 13q32. However, esophageal atresia is a rare symptom and the relevant region is unknown. Thus, determining the association between accurate breakpoints and new clinical features is essential.

Case presentation

A 28-year-old Japanese primigravid woman was referred for fetal growth restriction, absence of a gastric bubble, cerebellar hypoplasia, overlapping fingers, and polyhydramnios at 31 weeks gestation. At 38 + 0 weeks, she delivered a 1774 g female infant. The infant presented with isolated esophageal atresia (Gross type A), Dandy–Walker malformation, right microphthalmia, left coloboma, overlapping fingers, pleurocentrum in the thoracic vertebrae, reduced anogenital distance, and hearing loss. Her karyotype was diagnosed as 46,XX,del(13)(q32.1–qter) by amniocentesis, but array comparative genomic hybridization after birth revealed the deletion of 13q31.3–qter. At 48 days after birth, the infant underwent surgery for esophageal atresia and was later discharged from the hospital at 7 months of age.

Conclusion

This case report and the literature reviews supports the previous findings on the pathological roles of haploinsufficiency of the ZIC2/ZIC5 in Dandy–Walker malformation and the EFBN2 haploinsufficiency in eye malformation and hearing loss. Furthermore, the possible involvement of IRS2, COLA1, and COLA2 in eye malformation were identified. This is the first case of 13q deletion syndrome with esophageal atresia (Gross A), but it may be a symptom of VATER/VACTER association (vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects), as in the previous cases. These symptoms might also be associated with EFBN2 haploinsufficiency, although further research is required.
A simple and efficient method for cytoplasmic production of human enterokinase light chain in E. coli
Authors: Ebrahimifard Mohammad , Forghanifard Mohammad Mahdi , Yamchi Ahad , Zarrinpour Vajiheh , Sharbatkhari Mahrokh
Published: December 2022

Human enterokinase light chain (hEKL) cDNA sequence was designed with the help of codon optimization towards Escherichia coli codon preference and ribosome binding site design and artificially synthesized with a thioredoxin fusion tag at the N-terminal and a five his-tag peptide at the C-terminal. The synthetic hEKL gene was cloned into the pET-15 expression vector and transferred into the three different expression strains of E. coli BL21(DE3), NiCo21, and SHuffle T7 Express. Different growth and induction conditions were studied using a statistical response surface methodology (RSM). Recombinant hEKL protein was expressed at high levels in soluble form with 0.71 mM IPTG after 4 h of induction at 25 °C. Autocatalytic process cleaved TRX tag with enterokinase recognition site by the impure hEKL and yielded the mature enzyme. The target protein was then purified to homogeneity (> 95%) by affinity chromatography. The activity of hEKL was comparable to the commercial enzyme. From 1 L culture, 80 mg pure active hEKL was obtained with the specific activity of 6.25 × 102 U/mg. Three main parameters that help us to produce the enzyme in the folded and active form are the type of strain, SHuffle T7 strain, TRX and histidine fusion tags, and growth conditions including the increase of OD of induction and IPTG concentration and the decrease of induction temperature.
Cross-corpus speech emotion recognition using subspace learning and domain adaption
Authors: Cao Xuan , Jia Maoshen , Ru Jiawei , Pai Tun-wen
Published: December 2022

Speech emotion recognition (SER) is a hot topic in speech signal processing. When the training data and the test data come from different corpus, their feature distributions are different, which leads to the degradation of the recognition performance. Therefore, in order to solve this problem, a cross-corpus speech emotion recognition method is proposed based on subspace learning and domain adaptation in this paper. Specifically, training set data and the test set data are used to form the source domain and target domain, respectively. Then, the Hessian matrix is introduced to obtain the subspace for the extracted features in both source and target domains. In addition, an information entropy-based domain adaption method is introduced to construct the common space. In the common space, the difference between the feature distributions in the source domain and target domain is reduced as much as possible. To evaluate the performance of the proposed method, extensive experiments are conducted on cross-corpus speech emotion recognition. Experimental results show that the proposed method achieves better performance compared with some existing subspace learning and domain adaptation methods.
Framing the mobility transition: public communication of industry, science, media, and politics in Germany
Authors: Drexler C. E. , Verse B. , Hauslbauer A. , Lopez J. , Haider S.
Published: December 2022

Background

Applying the Multi-Level Perspective (MLP) on socio-technical transitions, paired with the interdisciplinary framing approach, this paper investigates how incumbent actors of automobility in Germany framed the issue of a "transition of mobility and transport" ("Verkehrs/Mobilitätswende") in their public communication in 2020. We first identified representatives of industry, science, policy, and media, since the Verkehrs/Mobilitätswende and its implementation measures are contested among these actors. Employing qualitative content analysis, we then screened 325 public documents according to the elements of the framing approach problem definition, causal interpretation, moral evaluation, and treatment recommendation.

Results

Findings show that most of the actors frame a transformation of transport and mobility as a necessity. Their arguments encompass environmental and climate-related issues as well as infrastructural problems for bikes and public transport caused by the hegemony of automobility. The actors propose a variety of solutions, primarily focusing on technical innovations for cars or on the expansion of different infrastructures to achieve a modal shift towards sustainable mobility.

Conclusion

This paper demonstrates that there is no common understanding of the problems and solutions to foster a mobility transition, as the diversity of problems and solutions proposed within the frame elements is high and complicates the prevailing implementation gap of the mobility transition. Therefore, MLP should be conceptually and methodologically bridged with the interdisciplinary framing approach, particularly with regard to the transition of mobility and transport.
Breast cancer risk factors in Iranian women: a systematic review and meta-analysis of matched case–control studies
Authors: Khoramdad Malihe , Solaymani-Dodaran Masoud , Kabir Ali , Ghahremanzadeh Neda , Hashemi Esmat-o-Sadat , Fahimfar Noushin , Omidi Zahra , Mansournia Mohammad Ali , Olfatbakh Asiie , Salehiniya Hamid , Haghighat Shahpar
Published: December 2022

Background

Identifying breast cancer risk factors is a critical component of preventative strategies for this disease. This study aims to identify modifiable and non-modifiable risk factors of breast cancer in Iranian women.

Methods

We used international databases (PubMed/Medline, Scopus, Web of Knowledge, and Embase) and national databases (SID, Magiran, and ISC) to retrieve relevant studies until November 13, 2022. The odds ratio (OR) with a 95% confidence interval using the random-effect model was used to estimate the pooled effect. The publication bias was assessed by the Egger and Begg test. A sensitivity analysis was conducted to evaluate the effect of each included study on the final measurement.

Results

Of the 30,351 retrieved articles, 24 matched case–control records were included with 12,460 participants (5675 newly diagnosed cases of breast cancer and 6785 control). This meta-analysis showed that of the known modifiable risk factors for breast cancer, obesity (vs normal weight) had the highest risk (OR = 2.17, 95% CI 1.47 to 3.21; I2 = 85.7) followed by age at marriage (25–29 vs < 18 years old) (OR = 2.00, 95% CI 1.53 to 2.61; I2 = 0), second-hand smoking (OR = 1.86, 95% CI 1.58 to 2.19; I2 = 0), smoking (OR = 1.83, 95% CI 1.41 to 2.38; I2 = 18.9), abortion history (OR = 1.44, 95% CI 1.02 to 2.05; I2 = 66.3), oral contraceptive use (OR = 1.35, 95% CI 1.11 to 1.63; I2 = 74.1), age at marriage (18–24 vs < 18 years old) (OR: 1.22, 95% CI 1.02 to 1.47; I2 = 0). Of non-modifiable risk factors, history of radiation exposure (OR = 3.48, 95% CI 2.17 to 5.59; I2 = 0), family history of breast cancer (OR = 2.47, 95% CI 1.83 to 3.33; I2 = 73), and age at menarche (12–13 vs ≥ 14 years old) (OR = 1.67, 95% CI 1.31–2.13; I2 = 25.4) significantly increased the risk of breast cancer.

Conclusions

Since most risk factors related to breast cancer incidence are modifiable, promoting healthy lifestyles can play an influential role in preventing breast cancer. In women with younger menarche age, a family history of breast cancer, or a history of radiation exposure, screening at short intervals is recommended.
TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis
Authors: Lépine Sarah , Castellanos-Montiel Maria José , Durcan Thomas Martin
Published: December 2022

Amyotrophic lateral sclerosis (ALS) is a disease characterized by upper and lower motor neuron (MN) loss with a signature feature of cytoplasmic aggregates containing TDP-43, which are detected in nearly all patients. Mutations in the gene that encodes TDP-43 (TARBDP) are known to result in both familial and sporadic ALS. In ALS, disruption of neuromuscular junctions (NMJs) constitutes a critical event in disease pathogenesis, leading to denervation atrophy, motor impairments and disability. Morphological defects and impaired synaptic transmission at NMJs have been reported in several TDP-43 animal models and in vitro, linking TDP-43 dysregulation to the loss of NMJ integrity in ALS. Through the lens of the dying-back and dying-forward hypotheses of ALS, this review discusses the roles of TDP-43 related to synaptic function, with a focus on the potential molecular mechanisms occurring within MNs, skeletal muscles and glial cells that may contribute to NMJ disruption in ALS.
“Your mind doesn’t have room for anything else”: a qualitative study of perceptions of cognitive functioning during and after recovery from anorexia nervosa
Authors: Keeler Johanna Louise , Konyn Carol Yael , Treasure Janet , Cardi Valentina , Himmerich Hubertus , Tchanturia Kate , Mycroft Hazel
Published: December 2022

Background

Past research has indicated the presence of cognitive difficulties in individuals with anorexia nervosa (AN), although it is unclear how these are experienced in real life. Moreover, it is unclear how and whether the experience of cognitive difficulties changes in nature and intensity over the course of the illness and following recovery.

Methods

Twenty-one female participants (AN = 11; recovered AN = 10) participated in online semi-structured interviews, utilising open-ended questions and exploring topics relating to their experiences of their cognitive function, changes over time and their perspectives on the future. Reflexive thematic analysis was conducted on the resulting transcripts.

Results

Six themes were identified, centred around the effects of the illness on mental and physical function, cognition, adaptation to living with the illness, similarities between AN and other psychopathology, tentative optimism for the future and recovery as a representation of liberation. Whilst respondents with AN appeared to perform remarkably well in their professional and educational lives, the cognitive difficulties were described as significantly impacting their ability to engage in life, particularly in the context of leisure and socialising. Respondents recovered from AN noted the importance of developing a non-AN identity as well as better emotion-regulation skills as central to recovery.

Conclusions

Whilst people with AN may be able to adapt their lives to the demands of the illness, they report significant cognitive difficulties that interfere with their engagement in many aspects of daily life. This should be considered by professionals working in the clinical management of AN. Treatments focused on ameliorating cognitive difficulties, and promoting emotional regulation and identity in AN are warranted.
#fitspiration: a comparison of the sport-related social media usage and its impact on body image in young adults
Authors: Klier Kristina , Rommerskirchen Tessa , Brixius Klara
Published: December 2022

Background

Following and posting sport-related content on social media is wide-spread among young people. To date, little is known about the interdependence between sport-related social media use and the thereby perceived personal body image.

Methods

We conducted an online survey (N = 285) to examine how social media influences the sport-related body image.

Results

In general, social media are frequently used for sport (n = 136, 47.7%). Resistance training correlated significantly with several motives of sport-related use of social media, and thus, represents the strong online presence of athletic sports. Less correlations could be found in team or other sports. Regarding the perception of body image, it was found that the group of rejecting (negative) body image significantly correlated with the emulation of social media mediated sport-related beauty and body ideals (r = 0.63, p = 0.001), as well as with increased body dissatisfaction when viewing sport-related posts on social media (r = 0.590, p = 0.001). Perceived social pressure and comparison were found to be mediators of the prevailing influence of social media usage.

Conclusions

These results reveal the importance of taking a closer look at socially shaped beauty and body ideals, especially in sport-related contents, striving for more educational campaigns such as Body Positivity and, above all, filtering information. Finally, future research is needed to gain deeper insight into young persons’ usage behavior of social media and its impact on the individual’s body image.

Trial Registration The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of University of the Federal Armed Forces Munich, Germany (01/24/2022).
Deamidation-related blood biomarkers show promise for early diagnostics of neurodegeneration
Authors: Wang Jijing , Zhang Ya-Ru , Shen Xue-Ning , Han Jinming , Cui Mei , Tan Lan , Dong Qiang , Zubarev Roman A. , Yu Jin-Tai
Published: December 2022

Background

The strongest risk factor of neurodegenerative diseases (NDDs) is aging. Spontaneous asparaginyl deamidation leading to formation of isoaspartate (isoAsp) has been correlated with protein aggregation in NDDs.

Methods

Two cohorts consisting of 140 subjects were studied. Cohort 1 contained patients with AD and healthy controls, while Cohort 2 recruited subjects with mild cognitive impairment (MCI), vascular dementia (VaD), frontotemporal dementia (FTD), Parkinson’s disease (PD) and healthy controls. The levels of isoAsp in plasma human albumin (HSA), the most abundant protein in plasma, as well as the levels of immunoglobulin G (IgG) specific against deamidated HSA were measured. Apart from the memory tests, plasma biomarkers for NDDs reported in literature were also quantified, including amyloid beta (Aβ) peptides Aβ40 and Aβ42, neurofilament light protein (NfL), glial fibrillary acidic protein (GFAP) and phosphorylated tau 181 (p-tau181) protein.

Results

Deamidation products of blood albumin were significantly elevated in vascular dementia and frontotemporal dementia (P < 0.05), but less so in PD. Intriguingly, the deamidation levels were significantly (P < 0.01) associated with the memory test scores for all tested subjects. Deamidation biomarkers performed superiorly (accuracy up to 92%) compared with blood biomarkers Aß42/Aß40, NfL, GFAP and p-tau181 in separating mild cognitive impairment from healthy controls.

Conclusion

We demonstrated the diagnostic capacity of deamidation-related biomarkers in predicting NDDs at the early stage of disease, and the biomarker levels significantly correlated with cognitive decline, strongly supporting the role of deamidation in triggering neurodegeneration and early stages of disease development. Prospective longitudinal studies with a longer observation period and larger cohorts should provide a more detailed picture of the deamidation role in NDD progression.
Evaluating contralateral neck failure in patients with lateralized OPSCC treated with transoral robotic surgery and neck management based on pre-operative SPECT-CT lymphatic mapping
Authors: Berania Ilyes , Hosni Ali , Thomas Carissa M. , Goldstein David , Bayley Andrew , Mohan Ravi , Hendler Aaron , Cooper Richard M. , de Almeida John R.
Published: December 2022

Background

Risk of contralateral nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) is relatively low, however, many OPSCC patients receive bilateral neck treatment. This study evaluates the oncological outcomes with management of the contralateral cN0 neck based on lymphatic mapping with single photon emission computed tomography (SPECT-CT).

Methods

Retrospective evaluation of patients with lateralized cT1-2 and contralateral cN0 OPSCC treated with primary surgery between December 2017 and October 2019. All patients underwent pre-operative lymphatic mapping using SPECT-CT. Clinical parameters including demographics, tumor characteristics and oncological outcomes were recorded.

Results

Thirteen patients underwent primary site resection with transoral robotic surgery (TORS) and ipsilateral neck dissection with or without adjuvant therapy. Twelve patients (92.3%) had ipsilateral drainage on SPECT-CT, whereas 1 (7.7%) patient had bilateral neck lymphatic drainage. Four patients (30.8%) underwent post-operative radiation therapy (PORT). Three patients with unilateral drainage on SPECT-CT underwent PORT with unilateral neck irradiation, and 1 patient with bilateral drainage underwent PORT with bilateral neck irradiation. Seven (53.8%) patients were staged as pT1, 6 (46.2%) patients as pT2, 6 (46.2%) patients were pN0, 3 (23.1%) patients were pN1, 1 (7.7%) patient was pN2a for and 3 (23.1%) patients were N2b. The median distance of the tumor from midline was 1.05 cm (0.0–1.58). Primary sites included tonsil (n = 10, 76.9%) and tongue base (n = 3, 23.1%). The median follow-up time was 15.4 months. All patients were disease free at the latest follow-up with no contralateral neck failures.

Conclusions

Pre-operative mapping of lymphatic drainage in early stage OPSCC with SPECT-CT is a promising tool which can reduce treatment to the contralateral neck potentially without compromising oncological outcomes.

Graphical Abstract
Whole body FDG PET/MR for progression free and overall survival prediction in patients with relapsed/refractory large B-cell lymphomas undergoing CAR T-cell therapy
Authors: Sjöholm Therese , Korenyushkin Alexander , Gammelgård Gustav , Sarén Tina , Lövgren Tanja , Loskog Angelica , Essand Magnus , Kullberg Joel , Enblad Gunilla , Ahlström Håkan
Published: December 2022

Background

To find semi-quantitative and quantitative Positron Emission Tomography/Magnetic Resonance (PET/MR) imaging metrics of both tumor and non-malignant lymphoid tissue (bone marrow and spleen) for Progression Free Survival (PFS) and Overall Survival (OS) prediction in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL) undergoing Chimeric Antigen Receptor (CAR) T-cell therapy.

Methods

A single-center prospective study of 16 r/r LBCL patients undergoing CD19-targeted CAR T-cell therapy. Whole body 18F-fluorodeoxyglucose (FDG) PET/MR imaging pre-therapy and 3 weeks post-therapy were followed by manual segmentation of tumors and lymphoid tissues. Semi-quantitative and quantitative metrics were extracted, and the metric-wise rate of change (Δ) between post-therapy and pre-therapy calculated. Tumor metrics included maximum Standardized Uptake Value (SUVmax), mean SUV (SUVmean), Metabolic Tumor Volume (MTV), Tumor Lesion Glycolysis (TLG), structural volume (V), total structural tumor burden (Vtotal) and mean Apparent Diffusion Coefficient (ADCmean). For lymphoid tissues, metrics extracted were SUVmean, mean Fat Fraction (FFmean) and ADCmeanfor bone marrow, and SUVmean, V and ADCmeanfor spleen. Univariate Cox regression analysis tested the relationship between extracted metrics and PFS and OS. Survival curves were produced using Kaplan–Meier analysis and compared using the log-rank test, with the median used for dichotomization. Uncorrectedp-values < 0.05 were considered statistically significant. Correction for multiple comparisons was performed, with a False Discovery Rate (FDR) < 0.05 considered statistically significant.

Results

Pre-therapy (p < 0.05, FDR < 0.05) and Δ (p < 0.05, FDR > 0.05) total tumor burden structural and metabolic metrics were associated with PFS and/or OS. According to Kaplan-Meier analysis, a longer PFS was reached for patients with pre-therapy MTV ≤ 39.5 ml, ΔMTV≤1.35 and ΔTLG≤1.35. ΔSUVmaxwas associated with PFS (p < 0.05, FDR > 0.05), while ΔADCmeanwas associated with both PFS and OS (p < 0.05, FDR > 0.05). ΔADCmean > 0.92 gave longer PFS and OS in the Kaplan-Meier analysis. Pre-therapy bone marrow SUVmeanwas associated with PFS (p < 0.05, FDR < 0.05) and OS (p < 0.05, FDR > 0.05). For bone marrow FDG uptake, patient stratification was possible pre-therapy (SUVmean ≤ 1.8).

Conclusions

MTV, tumor ADCmeanand FDG uptake in bone marrow unaffected by tumor infiltration are possible PET/MR parameters for prediction of PFS and OS in r/r LBCL treated with CAR T-cells.

Trial registration

EudraCT 2016–004043-36.
Orchiectomy due to delayed severe scrotal hematocele after laparoscopic transabdominal preperitoneal repair for a giant inguinoscrotal hernia: a case report
Authors: Nakamura Kenichi , Shibasaki Susumu , Takenaka Masashi , Serizawa Akiko , Akimoto Shingo , Nakauchi Masaya , Tanaka Tsuyoshi , Inaba Kazuki , Shiroki Ryoichi , Uyama Ichiro , Suda Koichi
Published: December 2022

Background

A giant inguinoscrotal hernia is a rare inguinal hernia that extends below the midpoint of the inner thigh while standing. Although reports of laparoscopic surgery for giant inguinoscrotal hernias have increased, the risk of delayed hematocele has not yet been clarified.

Case presentation

A 68-year-old man was evaluated for a left giant inguinoscrotal hernia, and laparoscopic transabdominal preperitoneal repair (TAPP) was performed. In the procedure, the distal hernia sac was not resected. The postoperative course was uneventful for 3 months postsurgery, after which he complained of giant scrotal swelling, which gradually grew to 13 cm. It did not improve with several punctures and caused dysuria because of increased pressure on the urethra. Thus, reoperation was performed 9 months after surgery. The hematocele consisted of a thickened hernia sac, which was tightly adhered to the spermatic cord and testicle. The hernia sac including the hematocele was removed from the scrotum through an anterior approach, preserving the spermatic cord and testicle. On the third postoperative day, an orchiectomy was performed due to poor testicular perfusion caused by spermatic cord injury. There was no hematocele or hernia at the 3-year follow-up. The remnant sac after laparoscopic TAPP for a giant inguinoscrotal hernia possibly caused refractory hematocele. Additionally, the removal of the hernia sac, including hematocele, from the spermatic cord and testicle has a risk of inducing injury, leading to orchiectomy.

Conclusion

Surgeons should be aware of the possibility of delayed refractory hematoceles after laparoscopic TAPP for giant inguinoscrotal hernias when the hernia sac is not resected.
Effect of a diet based on the dietary guidelines for americans on inflammation markers in women at risk for cardiometabolic disease: results of a randomized, controlled trial
Authors: Krishnan Sridevi , Freytag Tammy , Jiang Xiaowen , Schuster Gertrud U. , Woodhouse Leslie R. , Keim Nancy L. , Stephensen Charles B.
Published: December 2022

Objective

To evaluate the effect of a diet pattern based on Dietary Guidelines for Americans (DGA), in a controlled feeding setting, on plasma markers of inflammation and on cytokine production by peripheral blood mononuclear cells (PBMC).

Design

Women (n = 44) with one or more risk factors of metabolic syndrome (and BMI: 25.2-39.8 kg/m2) completed an 8-wk controlled feeding study. They were randomized to either a group following a diet based on DGA 2010 (DGA), or a group given a ‘typical American diet’ (TAD), based largely on a Western diet pattern. By design, women maintained their body weight. Fasting plasma and PBMC were collected at wk. 0 (baseline) and at wk. 8 (post-intervention). Sixteen plasma markers of inflammation and eight PBMC cytokines were measured at both time points, to evaluate if the diet had a significant effect on concentrations of these inflammatory markers. Data were analyzed using ANCOVA, followed by multiple-comparison adjustment using Benjamini-Hochberg method.

Results

Significant changes observed in Serum Amyloid A (SAA) and Matrix Metalloproteinase 3 (MMP3) in plasma did not retain significance upon multiple comparison adjustment. SAA: p = 0.044, adj p = 0.450; DGA mean change [95% CI] = − 12.6[− 32.3 to 7.04]; TAD mean change [95% CI] = − 2.24 [− 9.99 to 5.51]. MMP3: p = 0.014, adj p = 0.35; DGA mean change [95% CI] = 2.72[− 4.16 to 9.59]; TAD mean change [95% CI] = − 0.98[− 16.7 to 14.7]). Other inflammation markers were not differently altered by DGA relative to TAD. Effect size of change (Cohens d) indicated a large/medium-large effect of intervention on MMP3 and CRP, and medium effect on IL-6.

Conclusions

No statistically significant changes were observed in the immune markers examined in this study. The biological roles and magnitude of the non-significant differences seen with two variables, CRP and MMP3, suggest that they be examined in future studies.

Trial registration

Clinicaltrials.gov identifier NCT02298725.
Describing the growth and nutritional status of sickle cell disease children and adolescents with reference to WHO growth standards in Cameroon
Authors: Charlotte Eposse Ekoube , Ritha Carole Mbono Betoko , Calixthe Ida Penda , Jeanne Georgette Mony Elimbi , Patricia Epee , Iyawa Hassanatou , Edgar Mandeng Ma Linwa , Michael Ngenge Budzi , Gaelle Ntsoli Kofane , Claudia Ekame Bulu Bianca , Dicka Sajida Misse , Paul Koki Ndombo , Daniele-Christiane Kedy Mangamba Koum
Published: December 2022

Background

Sickle cell disease (SCD) is a chronic disease with many complications among which is growth retardation. Here, we described the growth and nutritional status patterns of children with SCD and adolescents living in Douala, Cameroon.

Methods

This cross-sectional study took place at the sickle cell treatment center of Douala Laquintinie Hospital from November 2015 to April 2016. The sociodemographic and anthropometric information of each SCD patient was determined, and then used for computing z-score indexes (weight for age, weight for height, body mass index for height, and height for age). The different indexes were used to determine the prevalence of malnutrition forms (stunting, wasting, underweight, and overweight/obesity) and compared to WHO standards by gender and age.

Results

A total of 208 children and adolescents participated in the study. The mean age was 8 years (±5) and the median age was 7 years. Males accounted for 53.4% of cases, giving a sex ratio of 1:1.1. The proportions of wasting, stunting, underweight, and overweight/obesity in the overall population were 7.1% (n = 15), 9.1% (n = 19), 3.6% (n = 5) and 3.3% (n = 7) respectively. In children under 5, wasting, stunting, underweight, and overweight/obesity were noted in 1.4% (n = 1), 9.5% (n = 7), 1.4% (n = 1), and 5.4% (n = 4) respectively. In patients aged 5 years and above, a proportion of 10.5% (n = 14) was wasted, 9.0% (n = 12) were stunted, 5.9% (n = 4) were underweight and 2.2% (n = 7) were overweight/obese. The growth curve of children under five in our study was superimposable to the WHO standard growth curve. In children older than 5 years, the left shift for stunting was more pronounced for boys compared to girls.

Conclusion

Nine percent of children and adolescents with SCD are stunted. The growth deficit appeared to be higher in patients aged 5 years and above, more particularly in boys than girls. Overweight/obesity was uncommon in our series. More robust research designs and statistical analyses are needed to confirm or refute these findings.
Artificial intelligence in nonalcoholic fatty liver disease
Authors: Mahzari Ali
Published: December 2022

Background

Nonalcoholic fatty liver disease (NAFLD) has led to serious health-related complications worldwide. NAFLD has wide pathological spectra, ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma. Artificial intelligence (AI), including machine learning and deep learning algorithms, has provided great advancement and accuracy in identifying, diagnosing, and managing patients with NAFLD and detecting squeal such as advanced fibrosis and risk factors for hepatocellular cancer. This review summarizes different AI algorithms and methods in the field of hepatology, focusing on NAFLD.

Methods

A search of PubMed, WILEY, and MEDLINE databases were taken as relevant publications for this review on the application of AI techniques in detecting NAFLD in suspected population

Results

Out of 495 articles searched in relevant databases, 49 articles were finally included and analyzed. NASH-Scope model accurately distinguished between NAFLD and non-NAFLD and between NAFLD without fibrosis and NASH with fibrosis. The logistic regression (LR) model had the highest accuracy, whereas the support vector machine (SVM) had the highest specificity and precision in diagnosing NAFLD. An extreme gradient boosting model had the highest performance in predicting non-alcoholic steatohepatitis (NASH). Electronic health record (EHR) database studies helped the diagnose NAFLD/NASH. Automated image analysis techniques predicted NAFLD severity. Deep learning radiomic elastography (DLRE) had perfect accuracy in diagnosing the cases of advanced fibrosis.

Conclusion

AI in NAFLD has streamlined specific patient identification and has eased assessment and management methods of patients with NAFLD.
Temporal variations in the atmospheric pressure curve in the Bydgoszcz area
Authors: Łaszyca Edward
Published: December 2022

Atmospheric pressure, the meteorological parameter describing pressure conditions in an area, was analysed based on daily values. The mean atmospheric pressure in the Bydgoszcz area in the examined multi-annual period from 1971 to 2010 was 1006.4 hPa. Comparison of the mean value of atmospheric pressure calculated for the periods from 1971 to 1990 and from 1991 to 2010 revealed bi-directional differences between them. The atmospheric pressure curve featured high year to-year variability in the examined 40-year period. In Bydgoszcz, there was a statistically insignificant downward trend in mean annual atmospheric pressure (0.2 hPa/10 years) from 1971 to 2010.
Nutrition, Weight Gain, and Length of Stay of the Nicu Infants Who were not Placed in their Mothers' Arms
Authors: Özkaya Ismail , Oysal Gözde
Published: December 2022

Most neonatal deaths in the world occur in low- and middle-income countries. It is possible to prevent at least two-thirds of these deaths with the right approaches and breast milk.
Setting and Sampling: One hundred infants, 59% male and 41% female, participated in the study. These babies were hospitalized in the Newborn Intensive Care Unit without being placed in their mothers' arms. Weight gain and hospitalization periods were followed according to the nutritional status of the babies.
While 54% of the patients were fed only with breast milk, 42% were mixed-fed with a combination of breast milk and formula, and 4% of the patients who did not have mothers’ milk were fed only with the formula. There was no statistically significant difference between the weight differences and rank averages of the babies according to the status of feeding (U=108.5, p=0.142). The discharge times of babies who are breastfed in the NICU are significantly higher than those who do not receive breastmilk. In other words, breastfeeding status in the NICU was found to affect the length of time that infants were hospitalized in the NICU (U=62, p < 0.05). This study examined the nutrition, weight gain and length of stay of NICU infants. Babies who are taken to intensive care without ever reaching their mother are a difficult group to evaluate. We have shown that even for NICU infants who are not placed in their mothers' arms, breast milk is quite superior in both weight gain and hospitalized stay. Early and advanced-pregnancies and cesarean births in all age groups, unfortunately, increase the risk of complications that may occur in the mother and baby after birth. The rapid weight gain of the baby with formula foods is not a health indicator.
Nutrition Education Intervention to Promote Nutrition Knowledge in Preschool Children at District of Leiria, Portugal
Authors: -Pontes Cátia Braga , Pratas Eunice , Novo Ângela , Domingues Bianca , Miguens Rebeca , Simões-Dias Sara
Published: December 2022

Several factors can influence children’s food choices and preferences. Food and nutrition education at school can therefore be the key to improving children’s nutrition knowledge, and consequently their eating behavior. To this end, several strategies seem effective, and the current difficulty lies in choosing the best methodology to implement.
To determine which intervention has the greatest impact on preschool children’s nutrition knowledge about vegetables: serious game, children’s story, children’s story associated with stickers, or food wheel.
This experimental study had the participation of 162 children, aged between 3 to 6 years, attending four public school institutions in the district of Leiria, Portugal. To increase children’s nutrition knowledge about vegetables, four interventions were carried out: digital game, children’s story, children’s story associated with stickers, and a food wheel. To assess the recognition of foods, identification of vegetables, and the functions of five vegetables (lettuce, tomato, carrot, cucumber, and red cabbage), two instruments were applied at three different times (at the start, conclusion, and 6 months after the intervention). The collected data were analyzed using IBM SPSS software.
There was an increase in nutrition knowledge both post-intervention and 6 months follow-up, compared to the initial moment. This increase was statistically significant (p <0.001) when evaluated overall. The intervention with the digital game “Veggies4myheart”, compared to the children’s story associated with stickers, proved to be more effective in increasing nutrition knowledge related to the vegetable's functions, 6 months after the intervention (p = 0.028). The four interventions were effective to promote nutrition knowledge about vegetables in preschool children. The interventions with the digital game or with the child’s story with stickers seem to be the most appropriate to increase knowledge about vegetable functions.
Low 25 Hydroxyvitamin D and High Leptin Level as Risk Factors of Metabolic Syndrome in Obese Women
Authors: Sundari Luh Putu Ratna , Purnawati Susy , Tunas I Ketut , Weta I Wayan
Published: December 2022

Obesity is associated with low vitamin D levels and high leptin levels. The aim of this study is to see if low vitamin D levels and high leptin levels are risk factors for metabolic syndrome in obese women.This study use case control study to observe the difference of leptin and vitamin D plasma level as risk factor of metabolic syndrome on obesity women. There are 34 obese women as the sample of study. Subject is divided randomly into 2 groups, where each of groups consists of 17 obese with syndrome metabolic case and 17 obese women as control. Each group was tested for its vitamin D and leptin level. The relationship between vitamin D and leptin levels and metabolic syndrome was then investigated using the Chi Square test, and logistic regression was taken to discover odds ratio (OR). The result is p=0.031 (p<0.05), and OR=5.25; CI 95% which means the group with low vitamin D has risk factors for metabolic syndrome by 5 times than the control group high vitamin D. It was obtained p=0.001 (p<0.05), and OR= 256; CI 95% means that the case group with high leptin is the risk factors of the occurred metabolic syndrome by 256 times than low level of leptin in control group. It is concluded that in this study there is a link between low vitamin D levels and high leptin levels as risk factors of metabolic syndrome found in obesity.