bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy Balance–Related Factors and Risk of Colorectal Cancer Expressing Different Levels of Proteins Involved in the Warburg Effect
Authors: Jenniskens Josien C.A. , Offermans Kelly , Simons Colinda C.J.M. , Samarska Iryna , Fazzi Gregorio E. , Smits Kim M. , Schouten Leo J. , Weijenberg Matty P. , Grabsch Heike I. , van den Brandt Piet A.
Published: December 2021

Background:

Energy balance–related factors [body mass index (BMI), waist circumference, physical activity] have been associated with colorectal cancer risk. Warburg effect activation via PI3K/Akt signaling is one of the proposed mechanisms. We investigated whether energy balance–related factors were associated with risk of Warburg subtypes in colorectal cancer.

Methods:

We investigated this using immunohistochemistry for six proteins involved in the Warburg effect (LDHA, GLUT1, MCT4, PKM2, P53, PTEN) on tissue microarrays of 2,399 incident colorectal cancer cases from the prospective Netherlands Cohort Study (ntotal = 120,852; nsubcohort = 5,000; aged 55–69 in 1986; 20.3 years follow-up). Data analyses included 3,911 subcohort members and 1,972 colorectal cancer cases with complete covariate data. Expression levels of all proteins were combined into a pathway-based sum score and categorized into three “Warburg subtypes” (Warburg-low/moderate/high). Multivariable Cox regression analyses were used to estimate associations of BMI, clothing size (waist circumference proxy), and physical activity with Warburg subtypes in colorectal cancer.

Results:

BMI and clothing size were positively associated with Warburg-moderate and Warburg-high colon cancer risk in men (Pheterogeneity = 0.192). In women, clothing size was positively associated with Warburg-low and Warburg-high colon cancer (Pheterogeneity = 0.005). Nonoccupational physical activity was inversely associated with Warburg-low and Warburg-moderate colon cancer in women (Pheterogeneity = 0.045), but positively associated with Warburg-high rectal cancer in men (Pheterogeneity = 0.089).

Conclusions:

The Warburg effect might be involved in associations between adiposity and colon cancer risk, though additional mechanisms could be at play in women as well. The inverse association between physical activity and colon cancer might be explained by mechanisms other than the Warburg effect.

Impact:

Further research is needed to reproduce these results and investigate possible additional mechanisms.
Transient Global Cerebral Hypoperfusion as a Characteristic Cerebral Hemodynamic Pattern in the Acute Stage after Combined Revascularization Surgery for Pediatric Moyamoya Disease: N-Isopropyl-P-[123I] Iodoamphetamine Single-Photon Emission Computed Tomography Study
Authors: Kanoke Atsushi , Fujimura Miki , Tashiro Ryosuke , Ozaki Dan , Tominaga Teiji
Published: December 2021

Introduction: Surgical revascularization prevents cerebral ischemic attack by improving cerebral blood flow (CBF) in both adult and pediatric patients with moyamoya disease (MMD). Uneven hemodynamic changes, including local cerebral hyperperfusion and remote ischemia, can cause delayed intracerebral hemorrhage and perioperative infarctions in adult MMD patients, but the characteristic hemodynamic pattern among pediatric MMD patients after revascularization surgery is poorly understood. Methods: This study included 16 consecutive pediatric MMD patients (age, 6–16 years; mean age, 11.3) undergoing superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-myo-synangiosis on 21 affected hemispheres. Perioperative management was conducted by aspirin administration and strict blood pressure control (110–130 mm Hg). We prospectively performed N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography on postoperative days (POD) 1 and 7 and analyzed the temporal changes in perioperative hemodynamics. Results: Four patients (19.0%, 4/21) exhibited immediate CBF improvement from POD 1, which was classified as “immediate redistribution pattern.” In contrast, 9 (42.9%, 9/21) demonstrated transient hemispheric global hypoperfusion at POD 1 and subsequent CBF improvement at POD 7, which was defined as “transient hypoperfusion pattern.” Although 8 patients, including 4 with “transient hypoperfusion pattern” (44.4, 4/9), developed mild transient neurological deterioration in the acute stage, it resolved in all 21 patients, and there were no permanent neurological deficits. Discussion/Conclusions: This study revealed that the “transient hypoperfusion pattern” after revascularization surgery is relatively common among pediatric MMD patients, and its outcome is favorable under strict perioperative management.
To Give or to Receive? The Role of Giver Versus Receiver on Object Tracking and Object Preferences in Children and Adults
Authors: Noles Nicholaus S. , Gelman Susan A. , Stilwell Sarah
Published: December 2021

For adults, ownership is a concept that rests on principles and connections that apply broadly – whether the owner is the self or someone else, and whether the self is giver or receiver. The present studies tested whether preschool children likewise treat ownership in this abstract fashion. In Experiment 1, 20 children and 24 adults were assigned to be either “givers” or “receivers.” They were then asked to identify which items they and the researcher owned. In Experiment 2, 20 children and 24 adults were asked which items they and the experimenter liked best. In both experiments, participants’ judgments were not influenced by their role (giver vs. receiver), but were more adult-like when reasoning about self-owned than other-owned objects. These data suggest that intuitions about property ownership are initially egocentric – biased toward linking objects to one’s self – and then extend to others over the course of development.
The Conflicted City
Authors: Tadié Jérôme
Published: December 2021

As a megacity, Jakarta has enjoyed mixed forms of residential neighbourhoods, in which the kampungs used to prevail. After a period of kampung rehabilitation, relocation programmes intensified in Jakarta in the 1980s, influenced by the Singaporean model and paradigmatic shifts in international policies for housing for the poor. As a reaction, various local NGO s have proposed alternative solutions to what can seem a hegemonic international trend. Starting from the imposition of international models for housing for the poor, this paper studies how local NGO s in Jakarta have tried to negotiate these hegemonic global shifts and to propose other types of solutions. It first analyses the context of urban transformation in the central zones and the eradication of several kampungs. It then addresses the NGO s’ alternative visions of the city and its future, before showing how these visions are deeply rooted in formal and informal networks specific to the Indonesian context.
Exploring the Possible Contributions of the African Palaver towards a Participatory Synodal Church
Authors: Ilo Stan Chu
Published: December 2021

This essay argues for a participatory synodal Church and the possible contributions of the African palaver as a model for participatory dialogue in the Roman Catholic Church. The African palaver is the art of conversation, dialogue, and consensus-building in traditional society that can be appropriated in the current search for a more inclusive and expansive participatory dialogue at all levels of the life of the Church. I will develop this essay first by briefly exploring some theological developments on synodality between the Second Vatican Council and Pope Francis and some of the contributions of the reforms of Pope Francis to synodality in the Church. Secondly, I will identify how the African palaver functions through examples taken from two African ethnic groups. I will proceed to show how the African palaver could enter into dialogue with other new approaches to participatory dialogue for a synodal Church.
Reading the Bible Together with Muslims: David as Sinner King and Repentant Prophet
Authors: Steenbrink† Karel A.
Published: December 2021

The Jewish, Christian and Muslim traditions share many stories. The narratives about Adam, Abraham, Moses, Solomon and many others are modelled one after the other. During the last decades much attention has been given to the ‘three religions of Abraham’ as sharing the heritage of that great biblical figure. This contribution concentrates on the stories of David in the three religions as expression of the one hermeneutic family. It pleads that Jews and Christians take the Muslim reinterpretation of their heritage serious.
The EU Global Human Rights Sanctions Regime: between Self Help and Global Governance
Authors: Tilahun Nathanael
Published: December 2021

By adopting a Global Human Rights Sanctions regime, the European Union took a new step in leveraging its power to respond to human rights violations globally. The regime has a general scope, and targets both state and non-state actors. This paper shows that this regime occupies a tension zone between two competing approaches to sanctions: a self-help approach that perceives sanctions as deriving authority from states’ sovereignty and subservient to their foreign policy, and a global governance approach that views sanctions as deriving authority from and bound by the objectives of specific international legal regimes they enforce. The tension between these approaches comes into stark view when constructing the listing criteria and policy objectives of the sanctions, which determine the scope of targets and duration of measures. Whether and how subsequent practice resolves this tension will be determined by certain legislative and interpretive moves by the EU Council and Court.
Studying Ibn Sīnā, Performing Abulafia in a Mid-Sixteenth-Century Prison: Emotional, Medical, and Mystical Bodies between Italy and Silesia
Authors: Jánošíková Magdaléna
Published: December 2021

Historians often address knowledge transfer in two ways: as an extension and continuation of an established tradition, or as the tradition’s modification in an act of individual reception. This article explores the tension between the two approaches through a case study of Eliezer Eilburg. It traces the footsteps of a sixteenth-century German Jew and his study of the late medieval Hebrew medical and mystical literature composed in the wider Mediterranean. As it uncovers the cultural, political, and social processes shaping knowledge transfer between various Jewish cultures and geographies, the article highlights the receiver’s individual agency. Under the thickly described intellectual traditions, it is the receiver’s lived experience that allows historians to grasp the impact of knowledge on the lives of premodern people—the impact on their body and its relation to the world and to God. Building this argument, this article problematizes the relationship between theory and practice.
On the Question of the Continuity of Saite Traditions in Dynasty 30 (Cambridge, Fitzwilliam Museum E.5.1909; Brooklyn, Brooklyn Museum 56.152)
Authors: Belova Galina Alexandrovna
Published: December 2021

When W.M. Flinders Petrie excavated the Palace of Apries he uncovered a limestone block with inscriptions on both sides. This block was published in 1909 and is now kept in the Fitzwilliam Museum in Cambridge. Bernard Bothmer first compared the Cambridge block to another one kept in the Brooklyn Museum. He emphasized that they correspond closely and that the representations differ only minutely. After Bothmer’s publication, both artifacts were considered as originally parts of a single structure. In this contribution the function of the monument of which this block was originally a part will be investigated. The proposed interpretation gives rise to a new reading of religious representations of the ancient Egyptians. It is not about overcoming the barriers of the underworld, but about the practical use of spirits. The texts tell us about the Egyptian belief in affiliating oneself with the spirit of an important person for using it for personal purposes.
Exploring the Effects of Implementing a Research-Based SSI Program on Students’ Understanding of SSI and Willingness to Act
Authors: Choi Yunhee , Lee Hyunju
Published: December 2021

This study aimed to examine the effects of a research-based SSI program on fostering students’ understanding of issues and their willingness to act. Twenty-five middle school students voluntarily participated in the program on the issue of artificial food additives over 6 months. The data were collected by means of interviews with the students, field notes, and students’ artifacts such as SSI maps and journals. Results indicated that students’ research experiences helped them widen their understanding of the issues and feel more connectedness to the issue and motivated to explore the hidden nature of the issue as they conducted their research. They found various stakeholders in the food industry and business network and discovered how individual stakeholders would be affected within the network. They also became aware of the inequality and injustice that arose in the network. In addition, their experience of executing research increased their confidence and willingness to act for resolving contentious issues.
說「藜蒿」
Authors: 魏 鋼強
Published: December 2021

「藜蒿」，野生草本，嫩莖可食，為南昌名蔬。「藜蒿」是方言俗寫，有的地區叫「蘆蒿」，其實就是「蔞蒿」（Artemisia selengensis）。但「藜蒿」的「藜」與《廣韻》落侯切的「蔞」（今音 lóu）讀音不符，且具蔞蒿義的「蔞」也未能在古代典籍中見到讀落侯切的堅強實例。比對不同方言「藜～蒿 / 蘆～蒿」和「驢」「廬」諸字語音的平行變化，可以確定「藜～蒿 / 蘆～蒿」來自《廣韻》力朱切的「蔞」。由於方言語音構造的制約，才有了「藜蒿」和「蘆蒿」這樣的音讀。從看似不規則的方言異讀出發，區分新舊層次，就能還原歷史語音構造，從新的視角窺見方言語音演變的清晰軌跡。
懷嶽片贛語咸山攝開口知系字元音高化現象考察
Authors: 徐 建
Published: December 2021

懷嶽片贛語咸山攝開口知系字元音往往高化，韻母今讀ɛn或en。東南方言中，咸山攝開口知三章組字元音高化存在閩粵型、吳湘型和客贛型的差別。懷嶽片贛語屬於客贛型，繼承自洪武移民時期的贛語，客贛方言咸山攝開口知三章組字元音高化可以追溯至唐宋時期。
論南方漢語的重行體標記「過」
Authors: 遠藤 雅裕
Published: December 2021

「過」可以構成「V過」短語，表示以V所指的位移方式跨越某處。包括臺灣海陸客語在內的南方漢語的這種短語亦可表示“為了修正或補償再做一次V所指的動作”，如，「寫過」表示“再寫一次”。這種「過」稱為重行體標記或補償體標記（簡稱“重行「過」”）。本文主要對以往的研究補充一些臺灣客語的共時層面和歷時層面的重行「過」的材料，並討論以海陸客語為中心的南方漢語的重行「過」的詞義以及語法化途徑。結論為：重行「過」的核心語義為“謂語動詞所指的動作行為從頭到尾做一遍，做得完善”，而“再做”義和“修正”義等是通過“語境引發的重新解釋”(Heine & Kuteva 2002:2) 而產生的。這有兩種途徑。一種是，「過」常與「重新」、「再」、「再過」等“再做”義副詞共現，構成「再V過」等格式，而在這個格式裡副詞的“再做”義沾染到「過」字上。另一種是，「V過」常用在需要通過再做已經做過的動作而加以修正的語境裡。這種語境會促使「過」獲得“再做”義和“修正”義。這種「過」有可能派生於南宋《朱子語類》中的“從頭到尾做一遍”義的「過」（楊永龍2001）。重行「過」具體的語法化步驟如下：(i)作為趨向補語表示跨越空間或時間；(ii)作為趨向補語和體標記，表示V所指的動作從頭到尾做一遍；(iii)作為體標記，表示為了修正或補償再做一次V所指的動作；(iv)作為體標記，只表示再做一次某種動作。
Measuring the Size of the U.S. Jewish Population: New Estimates from a Pew Research Center Survey of Jewish Americans
Authors: Hackett Conrad , Ausubel Jacob
Published: December 2021

This paper presents new estimates of the U.S. Jewish population based on a 2019–2020 Pew Research Center survey, which used a stratified address-based sample of all Americans to screen more than 68,000 respondents and complete full interviews with more than 5,800 adults who are Jewish or have some kind of connection to Judaism. We estimate there are about 5.8 million adult Jews living in the United States, including 4.2 million who identify as Jewish by religion and 1.5 million who are Jews of no religion. In addition, 1.8 million children live with at least one adult Jew and are being raised Jewish in some way. Altogether, about 7.5 million people, or 2.4% of the total U.S. population, are Jewish. We present population estimates for additional detailed categories of Jewish adults and children in Jewish households that are not available in any other recent source.
Projecting Global Religious Populations, 2020–50
Authors: Johnson Todd M. , Crossing Peter F.
Published: December 2021

This article presents a series of projections for religious communities worldwide from 2020 to 2050. It offers details related to the projection methodology used to generate the estimates and comments on trends and patterns among Christians, Muslims, Hindus, Buddhists, agnostics, and atheists. It concludes with suggestions on how such projections might be improved in the future.
A new species of the Gekko japonicus group (Squamata: Gekkonidae) from Khammouane Province, central Laos
Authors: SITTHIVONG SALY , VAN LO OANH , NGUYEN TRUONG QUANG , NGO HANH THI , KHOTPATHOOM THANANH , LE MINH DUC , ZIEGLER THOMAS , LUU VINH QUANG
Published: December 2021

A new species of the Gekko (Japonigekko) japonicus group from Khammouane Province, central Laos is described based on morphological characters and molecular evidence. Morphologically, Gekko khunkhamensis sp. nov. can be distinguished from the remaining congeners by a combination of the following characters: size moderate (SVL 69.7–75.2 mm); nares in contact with rostral; internasals absent; postmentals enlarged; interorbital scales between anterior corners of the eyes 31 or 32; dorsal tubercles absent; ventrals between mental and cloacal slit 181–185; midbody scales 127–138; ventral scales 42–45; subdigital lamellae on first toe 13 or 14, on fourth toe 14 or 15; tubercles on upper surface of fore and hind limbs absent; precloacal pores absent in the male and females; postcloacal tubercles 2; tubercles absent on dorsal surface of tail base; subcaudals distinctly enlarged; dorsal surface of body with five dark grey bands, which become irregular posteriorly. Genetically, the new species is placed in a clade, consisting of G. bonkowskii, G. nadenensis, G. scientiadventura, G. sengchanthavongi, and G. thakhekensis and differs from other congeners by at least 13% in terms of pairwise distance based on a fragment of the mitochondrial ND2 gene.
Transoral Complete vs Partial Excision of the Sublingual Gland for Plunging Ranula
Authors: Roh Jong‐Lyel
Published: December 2021

Objectives

Plunging ranula is a pseudocyst of saliva extravasated from the sublingual gland (SLG) to the submandibular space. This is treated by transoral excision of the SLG or transcervical cyst excision that might differently affect surgical morbidity and recurrence. This study compared the clinical outcomes of complete vs partial excision of the SLG for plunging ranula.

Study Design

A nonrandomized comparative study.

Setting

Academic medical center.

Methods

This study included 42 patients with plunging ranula who underwent complete or partial excision of the SLG with the evacuation of cystic content. Two surgical methods of complete or partial SLG resection were alternatively allocated to consecutive patients without randomization. The primary outcome was a postoperative recurrence. Secondary outcomes were operation time and complications.

Results

Complete and partial excision of the SLG was performed in 22 and 20 patients, respectively, without injury to the Wharton’s duct or the lingual nerve. Postoperative complications in 42 patients were minor with temporary events: hematoma, 1 (5%); tongue numbness, 2 (5%); dysgeusia, 4 (9%); and dysphagia, 2 (5%), which did not differ between patients with complete and partial excision of the SLG (P >. 1). However, recurrence occurred in only 5 of 20 patients with partial SLG excision but none of 22 patients with complete SLG excision for a median follow‐up of 36 months.

Conclusions

Complete SLG excision is preferred over partial SLG excision to treat plunging ranula for reducing postsurgical risks of complications and recurrence.
Risk factors for delirium in adult patients receiving specialist palliative care: A systematic review and meta-analysis
Authors: Featherstone Imogen , Sheldon Trevor , Johnson Miriam , Woodhouse Rebecca , Boland Jason W , Hosie Annmarie , Lawlor Peter , Russell Gregor , Bush Shirley , Siddiqi Najma
Published: December 2021

Background:

Delirium is common and distressing for patients receiving palliative care. Interventions targetting modifiable risk factors in other settings have been shown to prevent delirium. Research on delirium risk factors in palliative care can inform context-specific risk-reduction interventions.

Aim:

To investigate risk factors for the development of delirium in adult patients receiving specialist palliative care.

Design:

Systematic review and meta-analysis (PROSPERO CRD42019157168).

Data sources:

CINAHL, Cochrane Database of Systematic Reviews, Embase, MEDLINE and PsycINFO (1980-2021) were searched for studies reporting the association of risk factors with delirium incidence/prevalence for patients receiving specialist palliative care. Study risk of bias and certainty of evidence for each risk factor were assessed.

Results:

Of 28 included studies, 16 conducted only univariate analysis, 12 conducted multivariate analysis. The evidence for delirium risk factors was limited with low to very low certainty.

Potentially modifiable risk factors:

Opioids and lower performance status were positively associated with delirium, with some evidence also for dehydration, hypoxaemia, sleep disturbance, liver dysfunction and infection. Mixed, or very limited, evidence was found for some factors targetted in multicomponent prevention interventions: sensory impairments, mobility, catheter use, polypharmacy (single study), pain, constipation, nutrition (mixed evidence).

Non-modifiable risk factors:

Older age, male sex, primary brain cancer or brain metastases and lung cancer were positively associated with delirium.

Conclusions:

Findings may usefully inform interventions to reduce delirium risk but more high quality prospective cohort studies are required to enable greater certainty about associations of different risk factors with delirium during specialist palliative care.
Genetically Modified Cell Transplantation Through Macroencapsulated Spheroids with Scaffolds to Treat Fabry Disease
Authors: Kami Daisuke , Suzuki Yosuke , Yamanami Masashi , Tsukimura Takahiro , Togawa Tadayasu , Sakuraba Hitoshi , Gojo Satoshi
Published: December 2021

Cell transplantation is expected to be another strategy to treat lysosomal diseases, having several advantages compared to enzyme replacement therapy, such as continuous enzyme secretion and one-time treatment to cure diseases. However, cell transplantation for lysosomal diseases holds issues to be resolved for the clinical field. In this study, we developed a new ex vivo gene therapy platform using a transplant pack, which consists of a porous membrane made of ethylene-vinyl alcohol in the pack-type and spheroids with scaffolds. These membranes have countless pores of less than 0.1 µm2 capable of secreting proteins, including alpha-galactosidase enzyme, and segregating the contents from the host immune system. When the packs were subcutaneously transplanted into the backs of green fluorescent protein (GFP) mice, no GFP-positive cells migrated to the transplanted pack in either autogenic or allogenic mice. The transplanted cells in the pack survived for 28 days after transplantation. When cells overexpressing alpha-galactosidase were used as donor cells for the packs and implanted into Fabry disease model mice, the accumulation of the alpha-galactosidase enzyme was also observed in the livers. In this study, we reported a new ex vivo therapeutic strategy combining macroencapsulation and cellular spheroids with scaffolds. This pack, macroencapsulated spheroids with scaffolds, can also be applied to other types of lysosomal diseases by modifying genes of interest.
Vibration response of glass fiber composite multi-layer graded corrugated sandwich panels
Authors: Yang Jin-Shui , Yang Fang , Han Liu , Yang Li-Hong , Wu Lin-Zhi
Published: December 2021

Based on the criteria of equal total height and relative density, a series of glass fiber composite multi-layer graded corrugated sandwich panels (MLGCSPs) with different configurations is designed and fabricated by an in-house hot-molding secondary molding method. The effects of arrangement modes, graded corrugated cores and corrugated topologies on the vibration behavior of the present MLGCSPs are comprehensively investigated by the vibration shaker tests. The results reveal that the arrangement modes, graded arrangement and topologies of the corrugated cores all have significant influences on the frequency responses, and vibration reduction of the present MLGCSPs. The arrangement mode II and III generally have significantly higher resonant frequencies and vibration attenuation performance in the low frequency range, but the arrangement mode I shows better vibration reduction and isolation performance in the higher frequency range. It is possible to simultaneously achieve higher fundamental frequency and lower amplitude of the structures by optimizing the arrangement mode and gradient configuration. Subsequently, finite element simulation is carried out to systematically analyze the vibration responses of the composite MLGCSPs with different configurations. The consistency between numerical and experimental results is quite well. Finally, the effects of structural parameters on the vibration characteristics of the present structures are also revealed. Some conclusions are obtained, which can provide some meaningful guidelines for the vibration reduction design of such type of multi-layer structures.
One-year post-operative comparison of visual function and patient satisfaction with trifocal and extended depth of focus intraocular lenses
Authors: Law Elizabeth M. , Aggarwal Rajesh K. , Buckhurst Hetal , Kasaby Hosam E. , Marsden Jonathan , Shum Gary , Buckhust Phillip J.
Published: December 2021

Purpose

To evaluate visual performance with trifocal and extended depth of focus IOL at 1 year post-operatively.

Setting

BMI Southend Hospital.

Design

Cohort study.

Methods

An age-matched cohort of forty subjects bilaterally implanted with the AT LISA 839MP trifocal IOL (20 patients, 40 eyes) and the Tecnis Symfony extended depth of focus IOL (20 patients, 40 eyes) were assessed at 3–6 months and 12–18 months post-operatively. Primary outcome measures were distance (6 m), intermediate (70 cm), near visual acuity (40 cm), and analysis of defocus profiles. Secondary outcomes included contrast sensitivity, Radner reading performance, quality of vision and assessment of halos.

Results

Distance visual acuity (VA) and defocus areas were similar ( p = 0.07). No significant difference in intermediate VA was noted but the intermediate area of focus was greater in the EDoF (0.31 ± 0.12 LogMAR*m−1) compared to the trifocal (0.22 ± 0.08LogMAR*m−1) ( p = 0.02). However, all near metrics were significantly better in the trifocal group. 80% of trifocal subjects were spectacle independent compared to 50% EDoF subjects. Quality of vision questionnaire found no significant differences between groups, however halo scores were greater at 3–6 months in the trifocal group ( p < 0.01) but no differences were noted at 12–18 months.

Conclusions

Near vision is significantly better for the trifocal, thus greater levels of spectacle independence. The range of intermediate vision was greater for the EDoF but no difference in intermediate VA. In the early period, differences in contrast sensitivity and halo size/intensity were noted, however, by one-year these measures were not significantly different.
Computational basis of decision-making impairment in multiple sclerosis
Authors: Fernández Rodrigo S , Crivelli Lucia , Pedreira María E , Allegri Ricardo F , Correale Jorge
Published: December 2021

Background:

Multiple sclerosis (MS) is commonly associated with decision-making, neurocognitive impairments, and mood and motivational symptoms. However, their relationship may be obscured by traditional scoring methods.

Objectives:

To study the computational basis underlying decision-making impairments in MS and their interaction with neurocognitive and neuropsychiatric measures.

Methods:

Twenty-nine MS patients and 26 matched control subjects completed a computer version of the Iowa Gambling Task (IGT). Participants underwent neurocognitive evaluation using an expanded version of the Brief Repeatable Battery. Hierarchical Bayesian Analysis was used to estimate three established computational models to compare parameters between groups.

Results:

Patients showed increased learning rate and reduced loss-aversion during decision-making relative to control subjects. These alterations were associated with: (1) reduced net gains in the IGT; (2) processing speed, executive functioning and memory impairments; and (3) higher levels of depression and current apathy.

Conclusion:

Decision-making deficits in MS patients could be described by the interplay between latent computational processes, neurocognitive impairments, and mood/motivational symptoms.
Smaller size is more suitable for pharmacotherapy among undersized abdominal aortic aneurysm: A systematic review and meta-analysis
Authors: Shirasu Takuro , Takagi Hisato , Yasuhara Jun , Kuno Toshiki , Kent K Craig , Clouse W Darrin
Published: December 2021

Background: Pharmacotherapy for undersized abdominal aortic aneurysm (AAA) is a clinical unmet need. Randomized controlled trials (RCTs) have failed to show effectiveness despite countless promising data in preclinical studies. We aimed to identify the population with undersized AAAs (30–54 mm) who potentially benefit from pharmacotherapy. Methods: In accordance with the PRISMA statement, we conducted a systematic review and meta-analysis of placebo-controlled RCTs. The primary outcome was mean difference (MD) in annual growth rate (< 0 favors pharmacotherapy), and the secondary outcome was aneurysm-related events (diameters ⩾ 55 mm, ruptures, or referral to surgery). Results: Our search strategy identified eight RCTs (six trials on antibiotics [ABx], two on renin-angiotensin system inhibitors [RAS-I]) with a total of 1325 patients. The mean of baseline diameters ranged from 33.1 mm to 43.1 mm. Neither ABx nor RAS-I showed significant differences in MD. Multivariable random-effects restricted maximum likelihood meta-regression revealed a statistically significant linear relationship between baseline diameter and MD (coefficient 0.15 [95% CI 0.0011, 0.30], p = 0.049) but not for the follow-up period ( p = 0.28) and duration of treatment ( p = 0.11). In line with this result, ABx with baseline diameter < 40 mm significantly reduced MD (−1.03 mm/year [95% CI −1.64, −0.42], p = 0.001) and a borderline significant difference in aneurysm-related events (HR 0.53 [95% CI 0.28, 1.00], p = 0.05), whereas the other groups ⩾ 40 mm never demonstrated effectiveness. Fixed-effect models did not change the results. No evidence of publication bias was detected. Conclusion: Undersized AAAs < 40 mm can potentially benefit from pharmacotherapy. Future RCTs should consider preferentially including undersized AAA with smaller diameters.
Preoperative nutritional score predicts underlying liver status and surgical risk of hepatocellular carcinoma
Authors: Umino Ryosuke , Kobayashi Yuta , Akabane Miho , Kojima Kazutaka , Okubo Satoshi , Hashimoto Masaji , Shindoh Junichi
Published: December 2021

Background:

Given the scarce evidence regarding the impact of preoperative nutritional status on surgical outcomes of patients with hepatocellular carcinoma, predictive powers of nutritional/inflammatory scores for short-term surgical outcomes in patients with hepatocellular carcinoma were investigated.

Methods:

Outcomes of 1272 patients with hepatocellular carcinoma were reviewed, and predictive powers of nine nutritional/inflammatory scores for short-term surgical outcomes were compared using the receiver-operating characteristic curve analysis. Clinical relevance of the best nutritional score was then studied in detail to clarify its utility as an alternative predictive measure for surgical risk of patients with hepatocellular carcinoma.

Results:

Receiver-operating characteristic curve analysis showed the controlling nutritional status score has the best performance in prediction of morbidity after hepatectomy for hepatocellular carcinoma (area under the curve, 0.593; 95% confidence interval: 0.552–0.635; p < 0.001), and multivariate analysis confirmed its correlation with the risk of any morbidity (odds ratio per +1 point, 1.17; 95% confidence interval: 1.08–1.27; p < 0.001) and major morbidity (odds ratio per +1 point, 1.14; 95% confidence interval: 0.99–1.27; p = 0.052). The undernutrition grade based on the controlling nutritional status score showed strong correlation with the degree of fibrosis in the liver ( p < 0.001), platelet count ( p < 0.001), and indocyanine green retention rate at 15 min ( p < 0.001). In addition, the controlling nutritional status undernutrition grade well stratified the risk of postoperative morbidity especially in cirrhotic subpopulation (odds ratio, 1.17 per +1 point; 95% confidence interval: 1.05–1.29 for any morbidity and odds ratio, 1.20 per +1 point; 95% confidence interval: 1.03–1.40 for major morbidity).

Conclusions:

The controlling nutritional status score could be an alternative measure for underlying liver injury and the surgical risk of hepatocellular carcinoma.
Cardamonin Promotes the Apoptosis and Chemotherapy Sensitivity to Gemcitabine of Pancreatic Cancer Through Modulating the FOXO3a-FOXM1 Axis
Authors: Sun Huapeng , Zhang Na , Jin Yiqiang , Xu Haisheng
Published: December 2021

Cardamonin (CAR), a flavone existing in the Alpinia plant, has been found to modulate multiple biological activities, including antioxidant, anti-inflammatory, and anti-tumor effects. Nevertheless, the influence of CAR on pancreatic cancer (PC) is less understood. Here, we conducted in vitro and in vivo experiments to explore the functions of CAR on PC cells’ proliferation, apoptosis and chemosensitivity to gemcitabine (GEM). The growth of PC cells (including PANC-1 and SW1990) was evaluated by the cell counting kit-8 assay, colony formation assay and xenograft tumor experiment. Besides, the apoptosis was determined by flow cytometry and western blot (WB). Moreover, the FOXO3a-FOXM1 pathway expression was tested by reverse transcription-polymerase chain reaction and WB. Our data suggested that CAR restrained cell proliferation, growth and expedited apoptosis both in vitro and in vivo. Moreover, CAR sensitized PC cells to GEM. Mechanistically, CAR heightened FOXO3a while repressed FOXM1. Further loss-of-function assays revealed that down-regulating FOXO3a markedly dampened the anti-tumor effect induced by CAR and accelerated the FOXM1 expression. Our data confirmed that CAR exerted an anti-tumor function in PC dependently by modulating the FOXO3a-FOXM1 axis.
Effect of practice hours on elite junior tennis players’ burnout: Gender differences
Authors: Mouelhi-Guizani Salma , Guinoubi Sarah , Teyeb Nessrine , Chtara Mokhtar , Crespo Miguel
Published: December 2021

This study investigated the effect of training hours on elite junior tennis players’ burnout with attention to gender differences. A quantitative cross-sectional design was used in this research. A sample of 70 junior elite Tunisian tennis players (17.01 ± 0.81y) completed a demographic and the Athlete Burnout Questionnaire. Results showed that 64% ( n = 45) had a low risk, 14% ( n = 10) had a moderate risk, 13% ( n = 9) showed a high risk of burnout and 9% ( n = 6) had burnout with individual differences. Analysis of variance revealed that players who trained more than 12 h (high volume) reported significantly higher scores of the burnout dimensions: emotional and physical exhaustion ( p < 0.001; d = 2.18); sport devaluation ( p < 0.001; d = 2.36); reduced sense of accomplishment ( p < 0.001; d = 2.27); as well general burnout ( p < 0.01; d = 2.69), than players that trained less than 12 h (moderate volume and low volume). The effect of gender was observed in the variables of emotional and physical exhaustion (t = 2.17; p < 0.03), sport devaluation ( t = 2.23; p < 0.029), reduced sense of accomplishment ( t = 2.58; p < 0.012) and general burnout ( t = 2.41; p < 0.019) with female players showing higher scores in all of the burnout dimensions. It was concluded that the high volume of weekly training hours by junior players was associated with higher levels of the general burnout scores and that female players showed higher burnout scores than their male counterparts.
Brain Networks Associated With COVID-19 Risk: Data From 3662 Participants
Authors: Abdallah Chadi G.
Published: December 2021

Background

Our behavioral traits, and subsequent actions, could affect the risk of exposure to the coronavirus disease of 2019 (COVID-19). The current study aimed to determine whether unique brain networks are associated with the COVID-19 infection risk.

Methods

This research was conducted using the UK Biobank Resource. Functional magnetic resonance imaging scans in a cohort of general population (n = 3662) were used to compute the whole-brain functional connectomes. A network-informed machine learning approach was used to identify connectome and nodal fingerprints that are associated with positive COVID-19 status during the pandemic up to February fourth, 2021.

Results

The predictive models successfully identified 6 fingerprints that were associated with COVID-19 positive, compared to negative status (all p values < 0.005). Overall, lower integration across the brain modules and increased segregation, as reflected by internal within module connectivity, were associated with higher infection rates. More specifically, COVID-19 positive status was associated with 1) reduced connectivity between the central executive and ventral salience, as well as between the dorsal salience and default mode networks; 2) increased internal connectivity within the default mode, ventral salience, subcortical and sensorimotor networks; and 3) increased connectivity between the ventral salience, subcortical and sensorimotor networks.

Conclusion

Individuals are at increased risk of COVID-19 infections if their brain connectome is consistent with reduced connectivity in the top-down attention and executive networks, along with increased internal connectivity in the introspective and instinctive networks. These identified risk networks could be investigated as target for treatment of illnesses with impulse control deficits.
Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome
Authors: Gerds Aaron T. , Scott Bart L. , Greenberg Peter , Lin Tara L. , Pollyea Daniel A. , Verma Amit , Dail Monique , Feng Yuning , Green Cherie , Ma Connie , Medeiros Bruno C. , Yan Mark , Yousefi Kasra , Donnellan William
Published: December 2021

We present primary results from the phase 1b GO29754 study evaluating the safety and tolerability of atezolizumab, a programmed death-ligand 1 inhibitor, alone and in combination with azacitidine, a hypomethylating agent (HMA), in patients with relapsed/refractory (R/R) or HMA-naïve myelodysplastic syndrome (MDS). Patients with R/R MDS received atezolizumab for 12 months (cohort A) or atezolizumab plus azacitidine for 6 cycles followed by atezolizumab as maintenance for 8 cycles (cohort B). Patients with HMA-naïve MDS received atezolizumab plus azacitidine until loss of clinical benefit (cohort C). Safety, activity, and exploratory end points were investigated. Forty-six patients were enrolled and received treatment (cohort A, n = 11; cohort B, n = 14; cohort C, n = 21). All patients experienced ≥1 adverse event (AE) on study, and all patients discontinued atezolizumab. In cohort A, 7 patients (63.6%) died, and no patients responded. In cohort B, 8 patients (57.1%) discontinued azacitidine, 11 (78.6%) died, and 2 (14.3%) responded. In cohort C, all 21 patients discontinued azacitidine, 13 died (61.9%), and 13 (61.9%) responded. The study was terminated by the sponsor before completion of recruitment because of the unexpected high early death rate in cohort C (6 [46.2%] of 13 deaths were due to AEs and occurred within the first 4 treatment cycles.). The high death rate and poor efficacy observed in this study do not support a favorable risk-benefit profile for atezolizumab as a single agent or in combination with azacitidine in R/R or HMA-naïve MDS. This trial was registered at www.clinicaltrials.gov as #NCT02508870.
Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001
Authors: Tran Thai Hoa , Langlois Sylvie , Meloche Caroline , Caron Maxime , Saint-Onge Pascal , Rouette Alexandre , Bataille Alain R. , Jimenez-Cortes Camille , Sontag Thomas , Bittencourt Henrique , Laverdière Caroline , Lavallée Vincent-Philippe , Leclerc Jean-Marie , Cole Peter D. , Gennarini Lisa M. , Kahn Justine M. , Kelly Kara M. , Michon Bruno , Santiago Raoul , Stevenson Kristen E. , Welch Jennifer J. G. , Schroeder Kaitlin M. , Koch Victoria , Cellot Sonia , Silverman Lewis B. , Sinnett Daniel
Published: December 2021

The molecular hallmark of childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent, prognostic genetic alterations, many of which are cryptic by conventional cytogenetics. RNA sequencing (RNA-seq) is a powerful next-generation sequencing technology that can simultaneously identify cryptic gene rearrangements, sequence mutations and gene expression profiles in a single assay. We examined the feasibility and utility of incorporating RNA-seq into a prospective multicenter phase 3 clinical trial for children with newly diagnosed ALL. The Dana-Farber Cancer Institute ALL Consortium Protocol 16-001 enrolled 173 patients with ALL who consented to optional studies and had samples available for RNA-seq. RNA-seq identified at least 1 alteration in 157 patients (91%). Fusion detection was 100% concordant with results obtained from conventional cytogenetic analyses. An additional 56 gene fusions were identified by RNA-seq, many of which confer prognostic or therapeutic significance. Gene expression profiling enabled further molecular classification into the following B-cell ALL (B-ALL) subgroups: high hyperdiploid (n = 36), ETV6-RUNX1/-like (n = 31), TCF3-PBX1 (n = 7), KMT2A-rearranged (KMT2A-R; n = 5), intrachromosomal amplification of chromosome 21 (iAMP21) (n = 1), hypodiploid (n = 1), Philadelphia chromosome (Ph)-positive/Ph-like (n = 16), DUX4-R (n = 11), PAX5 alterations (PAX5 alt; n = 11), PAX5 P80R (n = 1), ZNF384-R (n = 4), NUTM1-R (n = 1), MEF2D-R (n = 1), and others (n = 10). RNA-seq identified 141 nonsynonymous mutations in 93 patients (54%); the most frequent were RAS-MAPK pathway mutations. Among 79 patients with both low-density array and RNA-seq data for the Philadelphia chromosome-like gene signature prediction, results were concordant in 74 patients (94%). In conclusion, RNA-seq identified several clinically relevant genetic alterations not detected by conventional methods, which supports the integration of this technology into front-line pediatric ALL trials. This trial was registered at www.clinicaltrials.gov as #NCT03020030.
The MDM2 antagonist idasanutlin in patients with polycythemia vera: results from a single-arm phase 2 study
Authors: Mascarenhas John , Passamonti Francesco , Burbury Kate , El-Galaly Tarec Christoffer , Gerds Aaron , Gupta Vikas , Higgins Brian , Wonde Kathrin , Jamois Candice , Kovic Bruno , Huw Ling-Yuh , Katakam Sudhakar , Maffioli Margherita , Mesa Ruben , Palmer Jeanne , Bellini Marta , Ross David M. , Vannucchi Alessandro M. , Yacoub Abdulraheem
Published: December 2021

Idasanutlin, an MDM2 antagonist, showed clinical activity and a rapid reduction in JAK2 V617F allele burden in patients with polycythemia vera (PV) in a phase 1 study. This open-label phase 2 study evaluated idasanutlin in patients with hydroxyurea (HU)-resistant/-intolerant PV, per the European LeukemiaNet criteria, and phlebotomy dependence; prior ruxolitinib exposure was permitted. Idasanutlin was administered once daily on days 1 through 5 of each 28-day cycle. The primary end point was composite response (hematocrit control and spleen volume reduction > 35%) in patients with splenomegaly and hematocrit control in patients without splenomegaly at week 32. Key secondary end points included safety, complete hematologic response (CHR), patient-reported outcomes, and molecular responses. All patients (n = 27) received idasanutlin; 16 had response assessment (week 32). Among responders with baseline splenomegaly (n = 13), 9 (69%) attained any spleen volume reduction, and 1 achieved composite response. Nine patients (56%) achieved hematocrit control, and 8 patients (50%) achieved CHR. Overall, 43% of evaluable patients (6/14) showed a ≥50% reduction in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (week 32). Nausea (93%), diarrhea (78%), and vomiting (41%) were the most common adverse events, with grade ≥ 3 nausea or vomiting experienced by 3 patients (11%) and 1 patient (4%), respectively. Reduced JAK2 V617F allele burden occurred early (after 3 cycles), with a median reduction of 76%, and was associated with achieving CHR and hematocrit control. Overall, the idasanutlin dosing regimen showed clinical activity and rapidly reduced JAK2 allele burden in patients with HU-resistant/- intolerant PV but was associated with low-grade gastrointestinal toxicity, leading to poor long-term tolerability. This trial was registered at www.clinincaltrials.gov as #NCT03287245.
A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML
Authors: Zeidan Amer M. , Boss Isaac , Beach C. L. , Copeland Wilbert B. , Thompson Ethan , Fox Brian A. , Hasle Vanessa E. , Hellmann Andrzej , Taussig David C. , Tormo Mar , Voso Maria Teresa , Cavenagh James , O’Connor Tim , Previtali Alessandro , Rose Shelonitda , Silverman Lewis R.
Published: December 2021

Evidence suggests that combining immunotherapy with hypomethylating agents may enhance antitumor activity. This phase 2 study investigated the activity and safety of durvalumab, a programmed death-ligand 1 (PD-L1) inhibitor, combined with azacitidine for patients aged ≥65 years with acute myeloid leukemia (AML), including analyses to identify biomarkers of treatment response. Patients were randomized to first-line therapy with azacitidine 75 mg/m2 on days 1 through 7 with (Arm A, n = 64) or without (Arm B, n = 65) durvalumab 1500 mg on day 1 every 4 weeks. Overall response rate (complete response [CR] + CR with incomplete blood recovery) was similar in both arms (Arm A, 31.3%; Arm B, 35.4%), as were overall survival (Arm A, 13.0 months; Arm B, 14.4 months) and duration of response (Arm A, 24.6 weeks; Arm B, 51.7 weeks; P = .0765). No new safety signals emerged with combination treatment. The most frequently reported treatment-emergent adverse events were constipation (Arm A, 57.8%; Arm B, 53.2%) and thrombocytopenia (Arm A, 42.2%; Arm B, 45.2%). DNA methylation, mutational status, and PD-L1 expression were not associated with response to treatment. In this study, first-line combination therapy with durvalumab and azacitidine in older patients with AML was feasible but did not improve clinical efficacy compared with azacitidine alone. ClinicalTrials.gov: NCT02775903.