bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of sporadic intracanalicular vestibular schwannomas: A critical review and International Stereotactic Radiosurgery Society (ISRS) practice guidelines
Authors: Balossier Anne , Sahgal Arjun , Kotecha Rupesh , Fariselli Laura , Gorgulho Alessandra , Levivier Marc , Ma Lijun , Paddick Ian , Pollock Bruce E , Sheehan Jason P , Suh John H , Yomo Shoji , Zhang Zhenwei , Regis Jean
Published: December 2023

Background

The choice of an appropriate strategy for intracanalicular vestibular schwannoma (ICVS) is still debated. We conducted a systematic review and meta-analysis with the aim to compare treatment outcomes amongst management strategies (conservative surveillance (CS), microsurgical resection (MR), or stereotactic radiosurgery (SRS)) aiming to inform guideline recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS).

Methods

Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2021 referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical studies or case series reporting a cohort of ICVS managed with CS, MR, or SRS. Primary outcome measures included tumor control, the need for additional treatment, hearing outcomes, and posttreatment neurological deficits. These were pooled using meta-analytical techniques and compared using meta-regression with random effect.

Results

Forty studies were included (2371 patients). The weighted pooled estimates for tumor control were 96% and 65% in SRS and CS series, respectively (P < .001). Need for further treatment was reported in 1%, 2%, and 25% for SRS, MR, and CS, respectively (P = .001). Hearing preservation was reported in 67%, 68%, and 55% for SRS, MR, and CS, respectively (P = .21). Persistent facial nerve deficit was reported in 0.1% and 10% for SRS and MR series, respectively (P = .01).

Conclusions

SRS is a noninvasive treatment with at least equivalent rates of tumor control and hearing preservation as compared to MR, with the caveat of better facial nerve preservation. As compared to CS, upfront SRS is an effective treatment in achieving tumor control with similar rates of hearing preservation.
Synthesis and characterization of iron clusters with an icosahedral [Fe@Fe12]16+ Core
Authors: Xu Gan , Cui Yun-Shu , Jiang Xue-Lian , Xu Cong-Qiao , Li Jun , Chen Xu-Dong
Published: December 2023

Iron-metal clusters are crucial in a variety of critical biological and material systems, including metalloenzymes, catalysts, and magnetic storage devices. However, a synthetic high-nuclear iron cluster has been absent due to the extreme difficulty in stabilizing species with direct iron−iron bonding. In this work, we have synthesized, crystallized, and characterized a (Tp*)4W4S12(Fe@Fe12) cluster (Tp* = tris(3,5-dimethyl-1-pyrazolyl)borate(1−)), which features a rare trideca-nuclear, icosahedral [Fe@Fe12] cluster core with direct multicenter iron−iron bonding between the interstitial iron (Fei) and peripheral irons (Fep), as well as Fep···Fep ferromagnetic coupling. Quantum chemistry studies reveal that the stability of the cluster arises from the 18-electron shell-closing of the [Fe@Fe12]16+ core, assisted by its bonding interactions with the peripheral tridentate [(Tp*)WS3]4− ligands which possess both S→Fe donation and spin-polarized Fe−W σ bonds. The ground-state electron spin is theoretically predicted to be S = 32/2 for the cluster. The existence of low oxidation-state (OS ∼ +1.23) iron in this compound may find interesting applications in magnetic storage, spintronics, redox chemistry, and cluster catalysis.
A Longitudinal Analysis of Flavored Cigar Use and Cigar Smoking Cessation Among US Adults
Authors: Buszkiewicz James H , Cook Steven , Oh Hayoung , Mukerjee Richa , Hirschtick Jana L , Fleischer Nancy L
Published: December 2023

Background

Flavorings in cigars increase their appeal, mask the harsh taste of tobacco, and may hinder successful cigar smoking cessation; however, limited evidence has examined whether flavors are associated with short- or long-term cigar smoking cessation.

Aims and Methods

Using restricted data from the Population Assessment of Tobacco and Health Study Waves 1–5, we examined whether flavored cigar use was associated with 30-day-plus and 1-year-plus cigar smoking cessation among US adults. Multivariable discrete-time survival models were fit to a nationally representative sample of US adult (18+) respondents who had a current, established cigar use, smoked five or more days in the past 30 days, and did not exclusively smoke traditional premium cigars at baseline. Models adjusted for age, sex, race and ethnicity, income, cigar and cigarette smoking intensity, and blunt use.

Results

At baseline, 44.6% of respondents (n = 674) were 18–34 years old, 75.0% were male, 56.7% were non-Hispanic White, 78.9% had household incomes of <$50,000, and 56.2% smoked flavored cigars. In fully adjusted models, flavored cigar use was associated with a lower risk of 30-day-plus (HR = 0.76, 95% CI = 0.60, 0.97) but not 1-year-plus cigar smoking cessation (HR = 0.81, 95% = 0.62, 1.05).

Conclusions

We found that flavored cigar use was associated with a lower risk of short-term but not long-term cigar smoking cessation. More work is needed to understand the dynamics of cigar smoking transitions, including initiation, cessation, and relapse, particularly in larger cohorts and among those who exclusively use cigars or dual-use cigars and cigarettes.

Implications

As local and some state jurisdictions continue to adopt partial or complete bans of flavored cigar products and the United States Food and Drug Administration considers a national ban of all characterizing flavors in cigars, there is a need for more longitudinal work examining the associations between flavorings in cigars and short and long-term cigar-smoking behaviors, including but not limited to initiation, cessation, intensity of use, and relapse, particularly in diverse cohorts.
Effect of fatty acid profiles in varying recipes of ready-to-use therapeutic foods on neurodevelopmental and clinical outcomes of children (6–59 months) with severe wasting: a systematic review
Authors: Nienaber Arista , Conradie Cornelia , Manda Geoffrey , Chimera-Khombe Bernadette , Nel Ettienne , Milanzi Edith B , Dolman-Macleod Robin C , Lombard Martani J
Published: December 2023

Context

In 2020, 13.6 million children under 5 years suffered from severe acute malnutrition (SAM)/wasting. Standard ready-to-use therapeutic foods (RUTFs) improve polyunsaturated fatty acid (PUFA) status but contain suboptimal amounts of omega-3 (n-3) PUFAs with unbalanced n-6-to-n-3 PUFA ratios.

Objectives

The aim was to compare the effects of RUTFs with different essential fatty acid contents on PUFA status, neurodevelopmental, and clinical outcomes (mortality, comorbidities, and recovery) of children with severe wasting.

Data Sources

Twelve databases, trial repositories, and article references with no publication limitations.

Data Extraction

Ten studies from randomized, quasi, and cluster-randomized controlled trials providing RUTFs as home treatment to children 6–59 months with SAM/wasting were included.

Data Analysis

Plasma phospholipid eicosapentaenoic acid content was higher in children receiving RUTF with altered essential fatty acid contents compared with standard RUTF (0.20 [0.15–0.25], P < 0.00001). Docosahexaenoic acid (DHA) status only improved in children receiving RUTF with added fish oil (0.33 [0.15–0.50], P = 0.0003). The Malawi Developmental Assessment tool (MDAT) global development and problem-solving assessment scores were higher in global assessment and gross motor domains in children receiving added fish oil compared with standard formulation (0.19 [0.0–0.38] and 0.29 [0.03–0.55], respectively). Children receiving high-oleic-acid RUTF (lowering the n-6:n-3 PUFA ratio of the RUTF) with or without fish oil had significantly higher scores in social domains compared with those receiving the standard formulation (0.16 [0.00–0.31] and 0.24 [0.09–0.40]). Significantly higher mortality risk was found in children receiving a standard formulation compared with RUTF with a lower n-6:n-3 PUFA ratio (0.79 [0.67–0.94], P = 0.008).

Conclusion

Although lowering n-6:n-3 PUFA ratios did not increase plasma DHA, it improved specific neurodevelopmental scores and mortality due to lower linoleic acid (high-oleic-acid peanuts), higher alpha-linolenic acid (altered oil), or both. Additional preformed n-3 long-chain PUFAs (fish oil) with RUTF improved the children’s DHA status, neurodevelopmental outcomes, and weight-for-height z score. More research is needed regarding cost, availability, stability, acceptability, and the appropriate amount of n-3 long-chain PUFAs required in RUTFs for the best clinical outcomes.

Systematic Review Registration

PROSPERO registration no. CRD42022303694.
Intangible capital and productivity: Firm-level evidence from German manufacturing
Authors: Kaus Wolfhard , Slavtchev Viktor , Zimmermann Markus
Published: December 2023

This article analyses the importance of intangible capital for firm productivity using comprehensive official firm-level data from German manufacturing. Both aggregate intangible investment and the share of investing firms increase over time. However, the distribution of intangible investment is heavily right-skewed, with many firms investing nothing or little and few investing a lot. This holds both for manufacturing overall and within narrowly defined industries. The group of top investors is highly persistent from year to year, and persistence increases over time. Production function estimations reveal a positive output elasticity of intangible capital which is small on average but increases substantially with firm-level intangible capital intensity. There are also effect heterogeneities by firm size and enterprise group membership, especially among high-intangible-intensive firms. Finally, considering intangibles as production factors reduces the measured dispersion of Total Factor Productivity (TFP), mainly by tightening the upper part of the TFP distribution.
Cryptococcus neoformans Infections Differ Among Human Immunodeficiency Virus (HIV)–Seropositive and HIV-Seronegative Individuals: Results From a Nationwide Surveillance Program in France
Authors: Paccoud Olivier , Desnos-Ollivier Marie , Cassaing Sophie , Boukris-Sitbon Karine , Alanio Alexandre , Bellanger Anne-Pauline , Bonnal Christine , Bonhomme Julie , Botterel Françoise , Bougnoux Marie-Elisabeth , Brun Sophie , Chouaki Taieb , Cornet Muriel , Dannaoui Eric , Demar Magalie , Desbois-Nogard Nicole , Durieux Marie-Fleur , Favennec Loïc , Fekkar Arnaud , Gabriel Frederic , Gangneux Jean-Pierre , Guitard Juliette , Hasseine Lilia , Huguenin Antoine , Le Gal Solène , Letscher-Bru Valérie , Mahinc Caroline , Morio Florent , Nicolas Muriel , Rouges Célia , Cateau Estelle , Persat Florence , Poirier Philippe , Ranque Stéphane , Roosen Gabrielle , Roux Anne-Laure , Sasso Milène , Lortholary Olivier , Lanternier Fanny ,   for the French Mycoses Study Group, Brieu N , Durand C , Bertei D , Bouchara J P , Pihet M , Bland S , Bru J P , Pulik M , Turdu F Le , Lefrand H , Ferrand M , Larrouy M , Nevez G , Quinio D , Bachelier M N , Coustumier A Le , Carmagnol F , Rivière B , Podac B , Augereau O , Emond J P , Bacri J L , Berthelot G , Dalle F , Vallee E , Bizet J , Noussair L , Herrmann J L , Brocard C , Guiffault P , Layet A , Morel A , Penn P , Gigandon A , Sendid B , Cornu M , Prades N , Fiacre T Benoit-Cattin A , Levy S , Pitsch A , Kiefer M H , Debourgogne A , Moquet O , Colot J , Courtellemont L , Poisson D , Laurens V , Martres P , Godineau N , Picot S , Chassagne C , Djibo N , Devallière R , Camin-Ravenne A M , Bissuel F , Janvier F , Eloy C , Fur A , Rezzouk L , Mazars E , Eloy O , Chachaty E , Mihaila L , Dellion S , Patey O , Thouvenot A , Limousin L , Desplaces N , Raguin G , Gits-Muselli M
Published: December 2023

Among 1107 cryptococcosis cases from the French surveillance network (2005–2020), the proportion of HIV-seronegative individuals has recently surpassed that of HIV-seropositive individuals. We observed marked differences in patient characteristics, disease presentations, cryptococcal antigen results, infecting species, and mortality according to HIV serostatus.
Localized Myxofibrosarcoma: A Retrospective Analysis of Primary Therapy and Prognostic Factors in 134 Patients in a Single Institution
Authors: Pogkas Athanasios , Reichardt Peter , Tunn Per-Ulf , Niethard Maya , Werner Mathias , Ghani Saeed
Published: December 2023

Background

Primary therapy of localized myxofibrosarcoma (MFS) remains controversial. Primary resection is complicated by a high rate of local recurrence, and the refractoriness to non-surgical treatment results in a higher risk of metastasis. The aim of the present study was to contribute the findings of a single sarcoma-specialized center and encourage investigating new treatment options.

Patients and Methods

We analyzed 134 patients treated with localized MFS in our center regarding prognostic factors defining overall survival, local recurrence, and metastasis. We focused on multimodal treatment of localized MFS: surgery, radiation, chemotherapy, hyperthermia, and isolated limb perfusion.

Results

The 5-year OS was 74.9%. From a total of 134 patients: 74 (55.2%) stayed disease free, 48 (35.8%) had a local recurrence (LR), and 23 (17.2%) developed a distant metastasis (DM). The 5-year LR-free survival (LRFS) and DM-free survival (DMFS) were 66.1% and 80.8%, respectively. Older age, tumor size (cT) cT ≥ 2, non-extremity localization, and distant metastasis were adverse predictive factors for OS. Performing an incision biopsy, surgery in a sarcoma-center, wide local excision or compartment-oriented excision, negative margins, and radiotherapy were positive predictive factors for LR. Tumor size cT ≥ 3 was a negative predictive factor for DM. Grading was a negative predictive factor for LR (G ≥ 2) and for DM (G3) in the multivariable analysis.

Conclusion

Adjuvant radiation had a positive impact on LRFS in all localized tumor stages, even in cT1 tumors. Chemotherapy did not have a significant impact on DMFS, regardless of tumor stage. Our findings indicate that myxofibrosarcoma may be a chemotherapy-resistant entity and a much closer monitoring is required, in case of neoadjuvant treatment.
Paediatric health system impact of an early respiratory viral season in Eastern Ontario, Canada: A descriptive analysis
Authors: Meng Lynn , Bruce Liam , Buba Melanie , McLean Connor , Bisnaire Lise , Farion Ken J , Samson Lindy , Thampi Nisha
Published: December 2023

Objectives

We examined trends in patient volumes and care intensity among children admitted with laboratory-confirmed respiratory viral infections over 5 years in Ottawa, following the most recent and intense respiratory viral season experienced throughout the Ontario paediatric health system.

Methods

This was a retrospective cohort study of patients at the Children’s Hospital of Eastern Ontario (CHEO) in Ottawa, who were diagnosed with a laboratory-confirmed respiratory viral infection in the first 72 h of admission between October 22, 2017 and March 25, 2023. Their admissions were stratified by age groups and level of care intensity, based on unit of admission and/or additional ventilatory needs, with Level 3 patients requiring intensive care unit admission, and evaluated for trends over six surveillance periods that began in Week 35 (early September) and ended in Week 34 (end-August) of the following year.

Results

During the surveillance period from August 28, 2022 to March 25, 2023, there was an early, steep and twofold increase in admissions due to respiratory viral infections compared to previous periods, driven largely by Respiratory Syncytial Virus and Influenza A. Despite similar age distributions, there was a larger volume of Level 2 and 3 admissions, and higher proportion of patients requiring Level 2 care intensity in inpatient medicine units (23.4% versus 10.4% in pre-pandemic years; P < 0.001).

Conclusions

The most recent viral season was associated with elevated volumes and higher inpatient acuity compared to previous years and underscores the need for additional operational and human health resources to support paediatric health systems through these predictable surge periods.
Incidence and psychiatric predictors of Long COVID beyond 3 months in a city-wide community sample in Texas
Authors: Tsai Jack , Grace Abigail , Kurian Anita
Published: December 2023

Background

Studies have emerged about a syndrome of persistent symptoms of Coronavirus Disease-2019 (COVID-19) infection called ‘Long COVID’, which have mostly focused on the first 3 months. This study examined rates and predictors of Long COVID symptoms lasting beyond 3 months (termed Long2 COVID).

Methods

A longitudinal cohort study using a population-based sample of 511 adults in San Antonio, Texas with laboratory-confirmed cases of COVID-19 were assessed for Long2 COVID. Inverse probability weighting was used.

Results

In the sample, 19.18–59.10% met criteria for Long2 COVID depending on the definition. In general, Long COVID symptoms decreased after 3 months with the notable exception of an observed increase in loss of taste and smell. White Hispanic (adjusted odds ratio (aOR) = 7.66; 95% confidence interval (CI) = 1.78, 32.87) background and baseline depression symptoms (aOR = 1.30; 95% CI = 1.03, 1.65) were predictive of Long2 COVID. Long2 COVID was also associated with greater anxiety symptoms 6 months after onset of COVID-19.

Conclusions

A sizable proportion report COVID-19 symptoms lasting more than 3 months and some symptoms even increased over time. Adults who are Hispanic white adults or have depression may be at greater risk for Long2 COVID. Further research is needed on why some adults experience Long COVID and how to reduce the duration of illness.
International scientific communication on COVID-19 data: management pitfalls understanding
Authors: Tzivian Lilian , Benis Arriel , Rusakova Agnese , Syundyukov Emil , Seidmann Abraham , Ophir Yotam
Published: December 2023

Background

During the pandemic, countries utilized various forms of statistical estimations of coronavirus disease-2019 (COVID-19) impact. Differences between databases make direct comparisons and interpretations of data in different countries a challenge. We evaluated country-specific approaches to COVID-19 data and recommended changes that would improve future international collaborations.

Methods

We compared the COVID-19 reports presented on official UK (National Health System), Israeli (Department of Health), Latvian (Center for Disease Prevention and Control) and USA (Centers for Disease Control and Prevention) health authorities’ websites.

Results

Our analysis demonstrated critical differences in the ways COVID-19 statistics were made available to the general and scientific communities. Specifically, the differences in approaches were found in the presentation of the number of infected cases and tests, and percentage of positive cases, the number of severe cases, the number of vaccinated, and the number and percent of deaths.

Conclusion

Findability, Accessibility, Interoperability and Reusability principles could guide the development of essential global standards that provide a basis for communication within and outside of the scientific community.
‘To the Queen’: Tennyson’s Politics
Authors: Shrimpton Nicholas
Published: December 2023

Though Tennyson is often referred to as ‘conservative’, he was, like the other members of his family, not a Tory but a Whig. The disappearance of the Whig Party in the 1870s has caused its distinctive views to be largely forgotten. Without an understanding of them, however, it is easy to miss or misinterpret the significance of the political statements made in Tennyson’s verse. His two poems called ‘To the Queen’, one first published in 1851 the other printed in 1873 as the epilogue to Idylls of the King, are important expressions of these ideas. The first would be quoted (by the Chancellor of the Exchequer, and at Tennyson’s suggestion) in Parliament during the Reform Bill debates of 1866–1867. The second is a troubled and urgently topical comment on the demise of the Whig political identity. As such, it suggests a political reading of Idylls of the King as a whole, in which the creation and dissolution of King Arthur’s Round Table has come, by 1873, to reflect the birth and death of the mode of government created by the Whig Reform Act of 1832 and destroyed, together with the party which had introduced it, by the new politics of the later 1860s.
Comparison of EULAR/PRINTO/PReS Ankara 2008 and 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis in children
Authors: Kaya Akca Ummusen , Batu Ezgi Deniz , Jelusic Marija , Calatroni Marta , Bakry Reima , Frkovic Marijan , Vinšová Nikol , Campos Reinan T , Horne AnnaCarin , Caglayan Sengul , Vaglio Augusto , Moroni Gabriella , Emmi Giacomo , Ghiggeri Gian Marco , Koker Oya , Sinico Renato Alberto , Kim Susan , Gagro Alenka , Matucci-Cerinic Caterina , Çomak Elif , Ekici Tekin Zahide , Arslanoglu Aydin Elif , Heshin-Bekenstein Merav , Acar Banu Celikel , Gattorno Marco , Akman Sema , Sozeri Betul , Palmblad Karin , Al-Mayouf Sulaiman M , Silva Clovis Artur , Doležalová Pavla , Merkel Peter A , Ozen Seza
Published: December 2023

Objective

Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis. The 2022 ACR/EULAR-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in paediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA.

Methods

Retrospective data of paediatric patients with GPA in 20 centres from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated.

Results

The study included 77 patients with GPA and 108 controls [IgA vasculitis (n = 44), Takayasu’s arteritis (n = 20), microscopic polyangiitis (n = 16), polyarteritis nodosa (n = 14), Behçet’s disease (n = 12), eosinophilic granulomatosis with polyangiitis (n = 1) and Cogan’s syndrome (n = 1)] with a median age of 17.8 and 15.2 years, respectively. Among patients with GPA, constitutional symptoms (85.7%) and ENT involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (P = 0.229 and P = 0.733, respectively).

Conclusion

In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly.
Steroid hormones in systemic sclerosis: associations with disease characteristics and modifications during scleroderma renal crisis
Authors: Collet Aurore , Sanges Sebastien , Ghulam Amjad , Genin Michaël , Soudan Benoît , Sobanski Vincent , Hachulla Eric , Dubucquoi Sylvain , Djobo Bodale , Espiard Stéphanie , Douillard Claire , Launay David
Published: December 2023

Objective

The renin-angiotensin-aldosterone system (RAAS) and glucocorticoids (GCs) are involved in vascular remodeling and fibrosis but have not been extensively studied in systemic sclerosis (SSc). Our aim was to investigate the RAAS and GC hormones in SSc patients.

Methods

Serum levels of renin (dosage and activity), aldosterone and its precursors (DOC, B, 18-OH-DOC, 18-OH-B), and GCs (cortisol, cortisone, 11-deoxycortisol, 18-OH-F) were assessed in 122 SSc patients and 52 healthy controls. After applying stringent inclusion criteria aimed at ensuring accurate hormone assessments (exclusion of interfering drugs, strict sampling conditions), we analysed RAAS hormones in 61 patients, and GCs in 96 patients. Hormone levels were compared between patients and controls; and associations with disease characteristics were assessed in patients.

Results

Regarding RAAS hormones, SSc patients displayed significantly lower aldosterone levels (although within normal range), similar renin levels, and higher B levels than controls. Abnormal RAAS hormone levels were associated with a more severe SSc phenotype (lung and skin fibrosis, heart and pulmonary vascular involvements, inflammation). Regarding GC hormones, SSc patients had higher levels of cortisol, 11-desoxycortisol (precursor) and 18-OH-F (metabolite) but lower levels of cortisone (inactive counterpart) than controls. RAAS hormone levels were assessed in five SSc patients before and during scleroderma renal crisis (SRC): concentrations varied considerably between patients, but consistently included normal/increased aldosterone levels and elevated renin levels.

Conclusion

RAAS and GC hormones are abnormally produced in SSc patients, especially in patients with severe SSc and during SRC. This could suggest a participation of these hormonal systems in SSc pathogenesis.
Efficacy and safety of belimumab in patients with lupus nephritis: a real-world retrospective observational study
Authors: Lin Sishi , Zhang Ji , You Xiaohan , Chen Bo , Liang Yan , Zhou Yin , Ding Xiaokai , Lv Yinqiu , Zhang Huidi , Su Bofeng , Bai Yongheng , Chen Chaosheng
Published: December 2023

Objectives

To evaluate the differences in efficacy and safety between lupus nephritis (LN) patients who received belimumab plus standard therapy and those who received only standard therapy in real world practice.

Methods

Patients diagnosed with LN at the First Affiliated Hospital of Wenzhou Medical University from November 2012 to July 2023 were identified, and eligible cases were divided into two groups according to whether they received additional treatment with belimumab during the course of the disease.

Results

A total of 1169 LN patients were identified from our follow-up database. In total, 112 patients receiving add-on treatment with belimumab (BLM group) and 112 control patients matched for relevant baseline characteristics were enrolled in this study. The median duration of treatment with belimumab was 13.82 [7.24, 20.29] months. Compared with the control group, the BLM group had more significant improvement in disease activity indicators such as serum albumin and complement levels, significantly lower B-cell count, immunoglobulin, and earlier first attainment of renal remission, but there was no significant improvement in renal function and kidney-related events or death during the 2-year follow-up period. In the BLM group, the treatment effect of belimumab was more prominent in patients with lower levels of proteinuria. The safety profile of belimumab treatment was favorable, with a lower incidence of respiratory tract infection in the BLM group than in the control group during the follow-up period (P = 0.015).

Conclusions

This real-world study revealed that add-on treatment with belimumab provided better disease remission, and the therapeutic effect was more significant in patients with lower proteinuria levels. In addition, it had a favorable safety profile and reduced the risk of respiratory tract infection.
Advances in Material-Based Strategies for Diabetic Bone Regeneration
Authors: Li Zheng , Yue Muxin , Zhou Yongsheng
Published: December 2023

Increased bone fragility and poor bone healing are common and serious complications of diabetes, especially in elderly patients. Long-term hyperglycemia often leads to serious infection and nonunion. Diabetes brings changes to bone microenvironment, including imbalanced immunity, disorder of macrophage polarization, deterioration of microvascular system, excessive advanced glycation end products, reactive oxygen species (ROS), local high levels of glucose, and great tendency to infection. The main traditional managements of diabetic bone involve oral medication and systematic drug administration, which exhibit limited therapeutic efficacy and accompanied side effects. Materials-based strategies have recently been potential alternatives for the treatment of diabetic bone diseases. In this review, we highlight the main material-based strategies for diabetic bone repair deficiency, including regulation of macrophages, elimination of excessive ROS, and resistance to bacterial infection. We also describe the future therapeutic designing approaches for smart biomaterials for diabetic bone regeneration, which would provide new ideas to protect bone health in patients with diabetes.
Blessings: when worlds collide
Authors: Mohyuddin David , Burton Daniel
Published: December 2023

For over 100 years, the English Courts have entertained applications by trustees for directions, including to bless proposed “momentous” exercises of powers. Recently, this jurisdiction has extended through judicial decisions to corporate office-holders. The jurisdiction has received increasing scrutiny, not least in relation to the vexed question of immunity, resulting in the Court of Appeal’s recent decision in Denaxe Ltd v Cooper [2023] EWCA Civ 752, a case concerning Blackpool Football Club. This article considers the jurisdiction’s origins and expansion, before concluding that there are cogent reasons for its continued existence in relation to both trusts and the corporate sphere.
Unravelling horizontal direct effect in EU law: the case of the fundamental right to paid annual leave between ‘myth’ and ‘practice’
Authors: Cecchetti Lorenzo
Published: December 2023

It is rather trendy to talk about the ‘horizontal effect’ of fundamental rights in a society where the dividing line between public and private power is increasingly blurred. However, as soon as one tries to define the exact meaning of horizontal effect and its conditions, several issues swiftly arise. This article explores the past, the present, and the future of the horizontal direct effect in the European Union (EU) legal order, by focusing on the application of this doctrine to the fundamental labour rights today protected in the Charter of fundamental rights. Most notably, with the approaching of the fifth birthday of Bauer and Max-Planck, by looking at the case of the fundamental right to paid annual leave under Article 31(2) of the Charter, this article aims at unravelling the actual meaning of the conditions for the horizontal direct effect of the EU fundamental rights and the actual perimeter of this direct effect. Although the effectiveness of minimum labour rights mandatorily enhanced by this case law should be welcomed, it is argued that the doctrine of the horizontal direct effect of EU fundamental rights seems still stuck between being a proper constitutional doctrine and a mere type of direct effect. It is also claimed, first, that horizontal direct effect is not a unitary phenomenon in EU law. In spite of the continuity in the ECJ’s technical reasoning, there is indeed a striking contrast between the language of ‘perfect equalisation’ of the Charter to the treaties and its actual approach to the assessment of the horizontal direct effect of fundamental (labour) rights. The ECJ’s case law analysis on the fundamental right to paid annual leave will prove this point. Secondly, it is suggested that horizontal direct effect can be defined as a sui generis, on-call, subsidiary, corollary, and ‘amputee’ doctrine, and we will offer some considerations on each of these features by reference to the Court’s practice under investigation. Thirdly, we suggest that the horizontal direct effect of fundamental (labour) rights relies more on the history and trajectory of the EU regulation of that specific right in the EU legal order rather than on the wording of the Charter’s provision or other technicalities.
The species problem in Artemia Leach, 1819 (Crustacea: Anostraca), a genus with sexual species and obligate parthenogenetic lineages
Authors: Asem Alireza , Gajardo Gonzalo , Hontoria Francisco , Yang Chaojie , Shen Chun-Yang , Rastegar-Pouyani Nasrullah , Padhye Sameer M , Sorgeloos Patrick
Published: December 2023

Parthenogenesis is an asexual reproduction mode characterized by the development of a female oocyte without fertilization. From an evolutionary perspective, parthenogenesis seems less successful than the predominant sexual mode, though there are groups in which both reproductive types exist, an example of which is the genus Artemia Leach, 1819. This salt-tolerant crustacean inhabiting hypersaline environments contains regionally endemic sexual species and obligate parthenogenetic groups with different ploidy levels, collectively referred to as Artemia parthenogenetica. Here, we discuss the difficulties of using a common species concept in Artemia Leach, 1819. While sexual species are widespread and fit the Biological Species Concept (BSC), which emphasizes reproductive isolation to maintain species genetic integrity or cohesiveness, it does not apply to uniparental organisms originating from sexual species with major meiotic changes. We show that different ploidy levels of parthenogenetic Artemia groups with uniform nuclear gene pools are maternally independent genetic entities (or cohesive), collectively and wrongly referred to as Artemia parthenogenetica. Thus, we conclude that ‘Artemia parthenogenetica’ is an invalid nominal specific name. Additionally, parthenogenetic Artemia groups cannot be considered a form of Artemia species (A. urmiana and/or A. sinica). In conclusion, we recommend using the term ‘parthenogenetic lineage(s)’ instead of ‘parthenogenetic population(s)’ to describe asexual Artemia group(s), because in modern population genetics and systematics, the term ‘population’ refers to interbreeding individuals with sexual reproduction. Furthermore, it clarifies that parthenogenetic lineages of Artemia are native to Mediterranean biodiversity.
The role of artificial intelligence and convolutional neural networks in the management of melanoma: a clinical, pathological, and radiological perspective
Authors: Yee Joshua , Rosendahl Cliff , Aoude Lauren G.
Published: December 2023

Clinical dermatoscopy and pathological slide assessment are essential in the diagnosis and management of patients with cutaneous melanoma. For those presenting with stage IIC disease and beyond, radiological investigations are often considered. The dermatoscopic, whole slide and radiological images used during clinical care are often stored digitally, enabling artificial intelligence (AI) and convolutional neural networks (CNN) to learn, analyse and contribute to the clinical decision-making. To review the literature on the progression, capabilities and limitations of AI and CNN and its use in diagnosis and management of cutaneous melanoma. A keyword search of the Medline database for articles relating to cutaneous melanoma. Full-text articles were reviewed if they related to dermatoscopy, pathological slide assessment or radiology. Through analysis of 95 studies, we demonstrate that diagnostic accuracy of AI/CNN can be superior (or at least equal) to clinicians. However, variability in image acquisition, pre-processing, segmentation, and feature extraction remains challenging. With current technological abilities, AI/CNN and clinicians synergistically working together are better than one another in all subspecialty domains relating to cutaneous melanoma. AI has the potential to enhance the diagnostic capabilities of junior dermatology trainees, primary care skin cancer clinicians and general practitioners. For experienced clinicians, AI provides a cost-efficient second opinion. From a pathological and radiological perspective, CNN has the potential to improve workflow efficiency, allowing clinicians to achieve more in a finite amount of time. Until the challenges of AI/CNN are reliably met, however, they can only remain an adjunct to clinical decision-making.
68Ga-Citrate PET/CT Imaging in the Diagnosis of Skull Base Osteomyelitis and Its Usefulness in the Assessment of Treatment Response
Authors: Johnson Hanna Elizabeth , Sunny Saumya Sara , Hephzibah Julie , Thomas Regi , Sundaresan Rajan
Published: December 2023

Purpose

68Ga-citrate PET/CT imaging in the diagnosis of skull base osteomyelitis (SBO) and its usefulness in the assessment of treatment response.

Methods

Eighteen patients underwent 68Ga-citrate PET/CT scans for suspected SBO for diagnosis/assessment of treatment response.

Results

Of 18 patients, 16 patients had a positive study for SBO, and 2 patients had a negative study. Scan findings were correlated with clinical, biochemical, microbiological, and radiological parameters.

Conclusion

68Ga-citrate PET/CT is a promising tool in the diagnosis and management of skull base osteomyelitis.
Transformation From Atypical to Anaplastic Metastatic Meningioma
Authors: Morcet-Delattre Robin , Meneret Pierre , Coue Olivier , Vauleon Elodie , Prigent Kevin
Published: December 2023

World Health Organization (WHO) grade III anaplastic meningioma is scarce. In this way, most studies compared WHO grade I and II. Otherwise, some authors are uncertain about using 18F-FDG as a diagnostic tool to estimate the WHO grade, especially high. We report the case from a man with a grading tumor evolution from WHO grade II atypical to grade III anaplastic metastatic meningioma. This turning point was imaged using 68Ga-DOTATOC and 18F-FDG. Diagnostic was confirmed by histology. The case underlines the unparalleled power of molecular imaging characterized by high sensitivity staging and spectacular avidity changing relationship with grading tumor evolution.
The influence of emotional context on emotional word processing in discourse comprehension: evidence from event-related potential
Authors: Li Jingwen , Sui Xue , Li Yutong
Published: December 2023

This research utilized event-related potential (ERP) recording technology to examine the effect of emotional context on the processing of emotional information in sentences. Three types of emotion-consistent discourse materials (neutral–neutral, positive–positive and negative–negative) were constructed to specifically express neutral, positive and negative emotions, respectively. Each discourse comprised two sentences, with the emotionally significant words embedded at the penultimate position of the second sentence. Participants were asked to read these texts, respond to reading comprehension questions and the ERP amplitude induced by the emotional words was recorded. The results indicated a tripartite interaction in the N400 and Late positive component amplitudes involving emotional context, emotional words and brain hemispheres, observed in both frontal and central brain regions. Notably, there was a significant difference in response to positive words between positive and negative contexts. The findings suggest that emotional context has a substantial effect on the processing of emotional words. Positive words, in comparison to negative ones, are more influenced by emotional context, particularly in the frontal and central regions of the brain.
Autophagy Restricts Tomato Fruit Ripening Via a General Role in Ethylene Repression
Authors: Kumaran Girishkumar , Pathak Pradeep Kumar , Quandoh Ebenezer , Mursalimov Sergey , Devi Jyoti , Alkalai-Tuvia Sharon , Leong Jia Xuan , Schenstnyi Kyrylo , Levin Elena , Üstün Suayib , Michaeli Simon
Published: December 2023

Autophagy, a cellular degradation pathway, and the phytohormone ethylene function in plant development, senescence, and stress responses. However, the manner of their interaction is mostly unknown. We reasoned that this may be revealed by studying autophagy in a climacteric fruit ripening context, for which ethylene is crucial. During ripening, fruits undergo softening, color change, toxic compound degradation, volatile production, and sugar assembly by fine-tuning synthesis and degradation of their cellular content. For autophagy activity assessment, we analyzed autophagy-related 8 (ATG8) lipidation and GFP-ATG8-labeled autophagosome flux in tomato fruit cells. Autophagy activity increased sharply from ripening initiation, climaxed at its middle stage, and declined towards its end, resembling ethylene production dynamics. Silencing the core-autophagy genesSlATG2,SlATG7, andSlATG4separately in mature fruits resulted in early ethylene production and ripening onset, which was abrogated by 1-methylcyclopropene (1-MCP), an ethylene signaling inhibitor. Beyond ripening, Arabidopsisatg5andatg7mutant seedlings exhibited elevated ethylene production and sensitivity to 1-Aminocyclopropane 1-carboxylic acid (ACC), ethylenès precursor, which induces autophagy. This research demonstrates that autophagy limits tomato fruit ripening via a general role in ethylene restriction, opening the path for a mechanistic understanding of autophagy-ethylene crosstalk and harnessing autophagy for fruit shelf-life extension.
Use of phase plate cryo-EM reveals conformation diversity of therapeutic IgG with 50 kDa Fab fragment resolved below 6 Å
Authors: Lin Hsin-Hung , Wang Chun-Hsiung , Wu Yi-Min , Huang Shih-Hsin , Lin Sam Song-Yao , Kato Takayuki , Namba Keiichi , Hosogi Naoki , Song Chihong , Murata Kazuyoshi , Yen Ching-Hsuan , Hsu Tsui-Ling , Wong Chi-Huey , Tu I-Ping , Chang Wei-Hau
Published: December 2023

While cryogenic electron microscopy (cryo-EM) is fruitfully used for harvesting high-resolution structures of sizable macromolecules, its application to small or flexible proteins composed of domains like immunoglobulin (IgG) remain challenging. Here, we applied single particle cryo-EM to Rituximab, a therapeutic IgG mediating cancer cell toxicity, to explore its solution conformations. We found Rituximab molecules exhibited aggregates in cryo-EM specimens contrary to its solution behavior, and utilized a non-ionic detergent to successfully disperse them as isolated particles amenable to single particle analysis. As the detergent adversely reduced the protein-to-solvent contrast, we employed phase plate contrast to mitigate the impaired protein visibility. Assisted by phase plate imaging, we obtained a canonical three-arm IgG structure with other structures displaying variable arm densities co-existing in solution, affirming high flexibility of arm-connecting linkers. Furthermore, we showed phase plate imaging enables reliable structure determination of Fab to sub-nanometer resolution from ab initio, yielding a characteristic two-lobe structure that could be unambiguously docked with crystal structure. Our findings revealed conformation diversity of IgG and demonstrated phase plate was viable for cryo-EM analysis of small proteins without symmetry. This work helps extend cryo-EM boundaries, providing a valuable imaging and structural analysis framework for macromolecules with similar challenging features.
A suicidal and extensively disordered luciferase with a bright luminescence
Authors: Dijkema Fenne Marjolein , Escarpizo-Lorenzana Marta Iglesia , Nordentoft Matilde Knapkøien , Rabe Hanna Christin , Sahin Cagla , Landreh Michael , Branca Rui Mamede , Sørensen Esben Skipper , Christensen Brian Søndergaard , Prestel Andreas , Teilum Kaare , Winther Jakob Rahr
Published: December 2023

Gaussia luciferase (GLuc) is one of the most luminescent luciferases known and is widely used as a reporter in biochemistry and cell biology. During catalysis GLuc undergoes inactivation by irreversible covalent modification. The mechanism by which GLuc generates luminescence and how it becomes inactivated are however not known. Here we show that GLuc unlike other enzymes has an extensively disordered structure with a minimal hydrophobic core and no apparent binding pocket for the main substrate, coelenterazine. From an alanine scan, we identified two Arg residues required for light production. These residues separated with an average of about 22 Å and a major structural rearrangement is required if they are to interact with the substrate simultaneously. We furthermore show that in addition to coelenterazine, GLuc also can oxidize furimazine, however, in this case without production of light. Both substrates result in the formation of adducts with the enzyme, which eventually leads to enzyme inactivation. Our results demonstrate that a rigid protein structure and substrate binding site are no prerequisites for high enzymatic activity and specificity. In addition to the increased understanding of enzymes in general, the findings will facilitate future improvement of GLuc as a reporter luciferase.

Significance statement

Enzymes are typically characterized by an overall globular structure with a hydrophobic core and a defined cavity for binding of substrate, containing the active site amino acid residues. Gaussia Luciferase is a widely used luminescent reporter with a very strong, albeit short-lived, flash of light due to rapid auto-inactivation. We show, using solution NMR, that while this luciferase shows some secondary structure elements held together by disulfide bonds this highly unusual enzyme is extensively disordered with essentially no hydrophobic core. Although the enzymatic mechanism remains unknown, we have identified two essential arginine residues but, in the structure, these do not point into a common active site. In spite of this, the enzyme has high substrate specificity suggesting that it undergoes major structural rearrangements upon binding of substrate.
CDC20 determines the sensitivity to spindle assembly checkpoint (SAC) inhibitors
Authors: Zheng Siqi , Raz Linoy , Zhou Lin , Cohen-Sharir Yael , Tian Ruifang , Wardenaar Rene , Broekhuis Mathilde , Rodriguez Maria Suarez Peredo , Wobben Soraya , van den Brink Anouk , Bakker Petra , Foijer Floris , David Uri-Ben
Published: December 2023

Spindle assembly checkpoint (SAC) inhibitors are a recently developed class of drugs that perturb the regulation of chromosome segregation during division, induce chromosomal instability (CIN), and eventually lead to cell death. While they are currently in clinical trials for solid cancers, biomarkers to predict the response to SAC inhibitors are still lacking. We recently reported that aneuploid cancer cells are preferentially sensitive to SAC inhibition. Here, we investigated the molecular determinants of the response to SAC inhibition that underlies the differential sensitivity of aneuploid cells to these drugs. We found that this response was largely driven by the expression of CDC20, a main activator of the anaphase-promoting complex (APC/C), rather than by APC/C itself. Mechanistically, we discovered that CDC20 depletion prolonged metaphase duration, diminished mitotic errors, and reduced sensitivity to SAC inhibition. Aneuploid cells expressed high levels of CDC20 and experienced shorter metaphases and multiple mitotic errors, resulting in increased long-term sensitivity to SAC inhibition. Our findings propose high CDC20 expression as a favorable biomarker for SAC inhibition therapy and as an aneuploidy-induced therapeutic vulnerability.