bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoplasmic Reticulum as a Therapeutic Target in Cancer: Is there
a Role for Flavonoids?
Authors: Aghakhani Ava , Hezave Mehrnoush Baradaran , Rasouli Asma , Saberi Rounkian Masoumeh , Soleimanlou Fatemeh , Alhani Arian , Sabet Eqlidi Nasim , Pirani Maryam , Mehrtabar Saba , Zerangian Nasibeh , Pormehr-Yabandeh Asiyeh , Keylani Kimia , Tizro Neda , Deravi Niloofar 
Published: March 2023

Abstract:
Flavonoids are classified into subclasses of polyphenols, a multipurpose
category of natural compounds which comprises secondary metabolites extracted from
vascular plants and are plentiful in the human diet. Although the details of flavonoid
mechanisms are still not realized correctly, they are generally regarded as antimicrobial,
anti-fungal, anti-inflammatory, anti-oxidative; anti-mutagenic; anti-neoplastic;
anti-aging; anti-diabetic, cardio-protective, etc. The anti-cancer properties of flavonoids
are evident in functions such as prevention of proliferation, metastasis, invasion, inflammation
and activation of cell death. Tumors growth and enlargement expose cells to
acidosis, hypoxia, and lack of nutrients which result in endoplasmic reticulum (ER)
stress; it triggers the unfolded protein response (UPR), which reclaims homeostasis or
activates autophagy. Steady stimulation of ER stress can switch autophagy to apoptosis.
The connection between ER stress and cancer, in association with UPR, has been
explained. The signals provided by UPR can activate or inhibit anti-apoptotic or apoptotic
pathways depending on the period and grade of ER stress. In this review, we will
peruse the link between flavonoids and their impact on the endoplasmic reticulum in
association with cancer therapy.
An Overview of CDK Enzyme Inhibitors in Cancer Therapy
Authors: Mounika Peddaguravagari , Gurupadayya Bannimath , Kumar Honnavalli Yogish , Namitha Bannimath 
Published: March 2023

Abstract:
The ability to address the cell cycle in cancer therapy brings up new medication development
possibilities. Cyclin-dependent kinases are a group of proteins that control the progression of the
cell cycle. The CDK/cyclin complexes are activated when specific CDK sites are phosphorylated. Because
of their non-selectivity and severe toxicity, most first-generation CDK inhibitors (also known as
pan-CDK inhibitors) have not been authorized for clinical usage. Despite this, significant progress has
been made in allowing pan-CDK inhibitors to be employed in clinical settings. Pan-CDK inhibitors'
toxicity and side effects have been lowered in recent years because of the introduction of combination
therapy techniques. As a result of this, pan-CDK inhibitors have regained a lot of clinical potential as a
combination therapy approach. The CDK family members have been introduced in this overview, and
their important roles in cell cycle control have been discussed. Then, we have described the current
state of CDK inhibitor research, with a focus on inhibitors other than CDK4/6. We have mentioned
first-generation pan-CDKIs, flavopiridol and roscovitine, as well as second-generation CDKIs, dinaciclib,
P276-00, AT7519, TG02, roniciclib, and RGB-286638, based on their research phases, clinical
trials, and cancer targeting. CDKIs are CDK4/6, CDK7, CDK9, and CDK12 inhibitors. Finally, we
have looked into the efficacy of CDK inhibitors and PD1/PDL1 antibodies when used together, which
could lead to the development of a viable cancer treatment strategy
Phyto Pharmaceutical Advances on Black Turmeric as a Functional Herb
Authors: Kaur Simranjeet , Chauhan Pratik N. , Junaid Ul Hamid  , Kaur Simran , Sharma Yashika 
Published: March 2023

Abstract:
Herbal medicine is one of humanity's oldest professions, and herbal medicine's therapeutic
efficacy has been recognised since the dawn of time. In many parts of India, herbal treatments
have been found to be effective in the treatment of malaria, diarrhoea, jaundice, diabetes,
cough, fever, snakebite, miscarriages, and gonorrhoea. Curcuma caesia is a perennial herb with
bluish-black rhizomes that is native to Northeast and Central India. In antioxidant, antiinflammatory,
and human tumour cell proliferation, inhibitory effects of the rhizomes of indigenous
Curcuma caesia were investigated in this work. According to Research, Inc., the global
curcumin market was worth USD 46.6 million, with North America being the largest regional
market and India being one of the largest curcumin producers. With a revenue-based compound
yearly growth rate (CAGR) of 14.8% throughout the projection period, Europe is predicted to be
the fastest-growing region, with the global market. Because of expanding scientific talent and a
large network of biotechnology and food chemistry applications, curcumin quality and quantity
are projected to improve in the future. The study emphasizes the importance of using the bioactive
components of curcuma caesia in nanotechnology, liposomes, niosomes, micelles, and cyclodextrin.
Potential Value of the Stretched Exponential and Fractional Order Calculus
Model in Discriminating Between Hepatocellular Carcinoma and Intrahepatic
Cholangiocarcinoma: An Animal Experiment of Orthotopic Xenograft Nude
Mice
Authors: Xie Jinhuan , Li Chenhui , Chen Yidi , Zhang Huiting , Lin Huashan , Yang Guang , Long Liling 
Published: March 2023

Background:
In clinical practice, Preoperative differentiation between hepatocellular carcinoma and intrahepatic cholangiocarcinoma is challenging but critical for treatment decisions.

Objective:
This study investigated the discriminatory power of the stretched-exponential model and fractional-order calculus model parameters for hepatocellular carcinoma versus intrahepatic cholangiocarcinoma in orthotopic xenograft nude mice.

Methods:
Prototype orthotopic xenograft models of hepatocellular carcinoma and intrahepatic cholangiocarcinoma were developed using 20 nude mice divided into two groups and separately transplanted with MHCC97H and HUCCT1 cells. Readout-segmented diffusion-weighted imaging with multiple b-values (0–2000 s/mm2) was obtained using a 3.0-T magnetic resonance imaging scanner. The apparent diffusion coefficient was calculated using the mono-exponential model. The distributed diffusion coefficient and intravoxel water molecular diffusion heterogeneity (α) were calculated using the stretched-exponential model. The diffusion coefficient (D), fractional-order derivative in space (β), and spatial parameter (μ) were calculated using the fractional-order calculus model. The liver and tumor specimens of nude mice were immunostained after euthanasia to clarify the liver cancer type. Differences in diffusion-related parameters between the groups were evaluated using Mann–Whitney U-test and univariate logistic analysis. Receiver operating characteristic curves were used to assess the diagnostic efficacy of each parameter. P<0.05 was deemed significant.

Results:
α, D, and β were significant discriminators between the groups. The area under the curve for these three variables was 0.890, 0.830, and 0.870, respectively, with cutoff values of 0.491, 0.435, and 0.782, respectively.

Conclusion:
The stretched-exponential model parameters α and the fractional-order calculus model parameters D and β showed high diagnostic efficacy in discriminating intrahepatic cholangiocarcinoma from hepatocellular carcinoma in orthotopic xenograft nude mouse models.
LCMS Determination and Cytotoxicity of Abrus precatorius on L6 and SK-N-MC
Cell Lines
Authors: Naduchamy Krishna Prabha , Parthasarathy Varadarajan 
Published: March 2023

Objective:
The present study aimed to investigate the cytotoxic effect of various extracts derived from Abrus
precatorius Linn. leaves on rat L6 and human SK-N-MC neuroblastoma cell lines and determine the secondary metabolites
responsible for the cytotoxicity of Abrus precatorius.

Methods:
Successive solvent extraction of A. precatorius leaves was carried out using the Soxhlet apparatus with solvents
such as petroleum ether, chloroform, ethyl acetate, and ethanol. HPTLC fingerprinting and LC-MS studies were
performed to assess the presence of secondary metabolites, such as flavonoids and phenols, in the ethyl acetate extract.
Furthermore, the cytotoxic effect of extracts was tested on rat skeletal muscle cell line L6 and human neuroblastoma
cell line SK-N-MC using MTT assay.

Results:
The total phenolic content of ethyl acetate and ethanol extracts of A. precatorius were 72.67 and 60.73 mg,
respectively, of GAE/g dry weight of the extract. The total flavonoid content of ethyl acetate and ethanol extract of A.
precatorius were 107.33 and 40.66 mg of Quercetin equivalents/g dry weight of the extract. LCMS analysis demonstrated
that the flavonoids in specific Naringenin, Diosmetin, Glycitin, and Genistein might play a prominent role in the
cytotoxicity of A. precatorius. The cytotoxicity study revealed that the extracts of A. precatorius were non-toxic to rat L6
myotubes, and the IC50 values of the various extracts, such as APPE, APCH, APEA, and APET, were >100 μg/ml. The
extracts exhibited cytotoxic activity against human neuroblastoma SK-N-MC cells, and the IC50 values of APPE, APCH,
APEA, APET, and the standard drug “Cisplatin” were >100, >100, 64.88, >100, and 3.72 μg/ml, respectively.

Conclusion:
It was concluded from the study that the extracts of Abrus precatorius were cytotoxic to neuroblastoma
cell lines but non-toxic to normal cell lines. HPTLC and LC-MS studies confirmed that flavonoids in the ethyl acetate
extract could be responsible for the biological activity.
Havana Syndrome: A Mysterious Illness or a New Domain of
Warfare
Authors: Nath Soumitra 
Published: March 2023

Abstract:
Havana syndrome cases increased in Cuba at the end of 2016 and early 2017, and the consequences
ranged from minor to severe health concerns. In almost all affected individuals, symptoms like
difficulty-concentrating, visual issues, brain-fog, memory problems, tinnitus, and sleep-related complaints
were reported. Some initial studies pointed the causative possibility towards energy weapons, ultrasound,
microwaves, microbes and chemicals. However, to date, no study has provided a comprehensive explanation
of this sudden mysterious syndrome, and the root cause remains unexplained.
Electronic Health Record–Nested Reminders for Serum Lithium Level Monitoring in Patients With Mood Disorder: Randomized Controlled Trial
Authors: Seki Tomotsugu , Aki Morio , Furukawa Toshi A , Kawashima Hirotsugu , Miki Tomotaka , Sawaki Yujin , Ando Takaaki , Katsuragi Kentaro , Kawashima Takahiko , Ueno Senkei , Miyagi Takashi , Noma Shun'ichi , Tanaka Shiro , Kawakami Koji 
Published: March 2023

Background
Clinical guidelines recommend regular serum lithium monitoring every 3 to 6 months. However, in the real world, only a minority of patients receive adequate monitoring.

Objective
This study aims to examine whether the use of the electronic health record (EHR)–nested reminder system for serum lithium monitoring can help achieve serum lithium concentrations within the therapeutic range for patients on lithium maintenance therapy.

Methods
We conducted an unblinded, single-center, EHR-nested, parallel-group, superiority randomized controlled trial comparing EHR-nested reminders with usual care in adult patients receiving lithium maintenance therapy for mood disorders. The primary outcome was the achievement of therapeutically appropriate serum lithium levels between 0.4 and 1.0 mEq/L at 18 months after enrollment. The key secondary outcomes are included as follows: the number of serum lithium level monitoring except for the first and final monitoring; exacerbation of the mood disorder during the study period, defined by hospitalization, increase in lithium dose, addition of antipsychotic drugs or mood stabilizers, or addition or increase of antidepressants; adherence defined by the proportion of days covered by lithium carbonate prescription during the study period.

Results
A total of 111 patients were enrolled in this study. A total of 56 patients were assigned to the reminder group, and 55 patients were assigned to the usual care group. At the follow-up, 38 (69.1%) patients in the reminder group and 33 (60.0%) patients in the usual care group achieved the primary outcome (odds ratio 2.14, 95% CI 0.82-5.58, P=.12). The median number of serum lithium monitoring was 2 in the reminder group and 0 in the usual care group (rate ratio 3.62; 95% CI 2.47-5.29, P<.001). The exacerbation of mood disorders occurred in 17 (31.5%) patients in the reminder group and in 16 (34.8%) patients in the usual care group (odds ratio 0.97, 95% CI 0.42-2.28, P=.95).

Conclusions
We found insufficient evidence for an EHR-nested reminder to increase the achievement of therapeutic serum lithium concentrations. However, the number of monitoring increased with relatively simple and inexpensive intervention. The EHR-based reminders may be useful to improve quality of care for patients on lithium maintenance therapy, and they have potentials to be applied to other problems.

Trial Registration
University Hospital Medical Information Network Clinical Trials Registry UMIN000033633; https://tinyurl.com/5n7wtyav
Tanzimat Dönemi Osmanlı Yol Çalışmaları Örnekleminde İnebolu Yolu Yapım Faaliyetleri (1862-1876)
Authors: BAZNA Alperen Yalçın 
Published: March 2023

Tanzimat Dönemi’nde eski kara yollarının çoğu bakımsızlıktan dolayı elverişsiz duruma düşmüştü. Bu nedenle Tanzimat Dönemi’nde şose yollar ile kara yolu ağlarında yeniden bir yapılanmaya gidildi. Çünkü merkezi hükümet, yolların bir devletin varlığını sürdürüp egemenliğini tesis etmesinde, iktisadi ve ekonomik gelişmeleri temin edip ülkenin mamur ve refahını arttırmasında oynadığı önemli rolü Avrupa’daki gelişmeleri de göz önünde bulundurarak daha iyi kavramıştı. Bu anlamda oluşturulan geçici imar meclislerinden ulaşıma öncelik verilmesi ve kara yolu ağlarının geliştirilmesi istendi. Ancak yol inşa faaliyetlerinin bir program dâhilinde yürütülmesi gerekiyordu. Bunun için Nafia Hazinesi, Nafia Nezareti ve bazı teknik kuruluşlar ihdas edilerek yapılacak şose yolların yapım faaliyetleri bir program dâhilinde ve kurallar çerçevesinde yürütülmeye çalışıldı.
Bu çalışmada ilk olarak İnebolu’dan Kastamonu’ya ancak daha sonra bazı zaruretlerle oradan da Çankırı’ya kadar uzatılmasına karar verilen İnebolu yolunun, şose ve toprak yol biçiminde yapım faaliyetleri ayrıntılı bir şekilde ele alınmıştır. Çalışmada bu yapım faaliyetlerinin ayrıntılı olarak ele alınmasının amacı yukarıda da belirtildiği üzere yolun bir ülkenin mukadderatına sağladığı avantajlar dışında inşa faaliyetleri esnasında ne gibi zorluklarla karşılaşıldığını ve bu gibi imar faaliyetlerinin hangi sebeplerden dolayı zamanında tamamlanmadığını arşiv kaynakları ışığında ortaya koymaktır.
Late Cretaceous to Early Cenozoic initiation of rifting of the Windhoek Graben, Namibia
Authors: Waren R. , Cartwright J. A. , Daly M.C. , Swart R. 
Published: March 2023

Abstract
The Windhoek Graben is a north-south trending rift in central Namibia that forms a prominent topographic feature bisecting an area of plateau uplift. It occupies a potentially crucial role in the propagation of the Late Cenozoic Southwest African Rift system regarding a possible continuation to the west of the Eiseb Rift. It is an unusual example of intra-continental rifting because it has no significant sediment fill associated with the period of active rifting, and hence the timing of rift activity and its tectonic relevance has not hitherto been established. To constrain the age of the Windhoek Graben we examine its regional geomorphic context and its relationship to four sites of igneous activity in the central Namibian Highlands. Two of these consist of clusters of eroded phonolitic tholoid bodies that have yielded 40Ar/39Ar dates of 32 Ma and 52 Ma, respectively, that we use to bracket the age of formation of a prominent remnant land surface, termed here the P52 Surface. From previous mapping of older intrusive igneous bodies, we argue that an even older land surface is partially preserved on the highest features in the area, and this surface (termed PRS) defines an initial domally uplifted surface from which initial drainage radiated, and onto which the earliest volcanic products associated with the Graben were erupted. In particular, the strong similarity in dyke and fault orientations is used to argue for a causal connection between the earliest magmatic activity and the onset of rifting. Long range correlation of PRS into the adjacent Aranos Basin strongly suggests a Late Cretaceous age for this earliest magmatic activity and the onset of rifting, but we cannot exclude a younger origin, any time up to the Early Eocene.
PENGARUH KARAKTERISTIK AGREGAT TERHADAP NILAI INDIRECT TENSILE STRENGTH PADA CAMPURAN LASTON
Authors: Yuniarti Ratna , Widianty Desi , Hasyim Hasyim , Mahendra Made , Alit Karyawan I Dewa Made , Salsabila Fera Fitri 
Published: March 2023

Pada konstruksi perkerasan jalan, agregat mempunyai proporsi yang sangat besar yaitu sekitar 90% terhadap berat campuran beraspal. Agregat harus memenuhi kriteria sesuai dengan persyaratan yang telah ditentukan karena kinerja konstruksi perkerasan jalan sangat tergantung dari karakteristik agregat yang digunakan. Tujuan dari tulisan ini adalah untuk menelaah hubungan antara karakteristik agregat terhadap nilai indirect tensile strength pada lapis aspal beton (laston). Agregat kasar yang digunakan dibedakan berdasarkan nilai aggregate impact value (AIV) serta variasi proporsi bentuk kubus dan pipih. Kajian karakteristik agregat tersebut meliputi berat jenis bulk, berat jenis kering permukaan jenuh, berat jenis semu, berat jenis efektif, penyerapan air dan tingkat kekerasan agregat. Berdasarkan analisa yang dilakukan dapat disimpulkan bahwa peningkatan nilai berat jenis bulk, berat jenis kering permukaan jenuh, berat jenis semu dan berat jenis efektif berdampak pada peningkatan nilai indirect tensile strength. Pada penyerapan air dengan rentang 1.80-3.11%, kemampuan campuran untuk menahan beban tarik semakin rendah seiring dengan semakin besarnya penyerapan air tersebut. Pada seluruh jenis dan komposisi agregat yang diujikan, semakin rendah tingkat keausan agregat menghasilkan nilai indirect tensile strength yang semakin tinggi. Secara umum karakteristik agregat berpengaruh kuat terhadap nilai indirect tensile strength.
Mental Health’s Address to the Challenging Cultural Reality of Malta
Authors: Galea Michael , Galea Frankline Zammit 
Published: March 2023

Appreciation of society as being the whole made up of so many different parts in terms of groups with various interests, skills and needs is what cultural diversity is about. Culture is defined as the distinctive customs, values, beliefs, knowledge, art and language of a society.
Multiculturalism has always been embedded with the Maltese reality. However, a steep increase in the country’s population since 2011 may be presenting new realities that can translate into hefty and challenging demands. This review therefore presents the following research-based evidence on how mental health can address this phenomenon, particularly in the case of Malta and similar small countries. In particular, the following aspects were highlighted, namely: cultural safety, holistic health services, multicultural awareness, sensitive lingual expression, community integrity and cultural partnership. Practical recommendations are presented.
Education Supplement for Genocide Awareness Month
Authors: Rich Jennifer 
Published: March 2023

Genocide Studies International ( GSI) is owned, operated, and managed by the International Institute for Genocide and Human Rights Studies (a division of the Zoryan Institute). The journal is published twice a year by the University of Toronto Press. Zoryan Institute, a nonprofit organization, serves the cause of scholarship and public awareness relating to issues of universal human rights, genocide, and diaspora-homeland relations. This is done through the systematic continued efforts of scholars and specialists using a comparative and multidisciplinary approach and in accordance with the highest academic standards.
Corporate Investment in Emerging Markets: The Role of Commodity Prices
Authors: Magud Nicolás E. , Sosa Sebastián 
Published: March 2023

We examine how firm-level and country-specific macroeconomic variables determine
corporate investment in emerging markets. In particular, we investigate how investment
decisions are affected by changes in country-specific commodity export prices, using
firmlevel data from 38 emerging markets for the period 1990–2013. We show that in
addition to the standard firm-level variables (such as expected future profitability,
cash flows, leverage, and new debt flows), commodity export prices play a significant
role in driving corporate investment. Moreover, we show that the sharp decline in
commodity prices since 2011 has been a key factor explaining the sizable slowdown in
private investment growth during this period, especially in regions with large net
commodity exporters. JEL Codes: E2, E3, F3, F4
The Short-Term Impact of Crime on School Enrollment and School Choice: Evidence
from El Salvador
Authors: Dahbura Juan Nelson Martínez 
Published: March 2023

This paper employs variations in crime rates, attributed to an unprecedented
countrywide truce between gangs in El Salvador in 2012, to evaluate the short-term
impact of homicides and extortions on the education choices of Salvadoran households.
Results reveal that the reduction in homicide rates due to the truce were associated
with a migration within the education system, from public to private institutions, among
boys aged fifteen to twenty-two years. The fluctuations in homicide rates were also
associated with a lower school attendance for girls aged seven to fourteen years,
especially due to a lower public school enrollment. No significant association between
fluctuations in extortion rates and education choices was observed. JEL
Codes: D13, I24, I25
The Effects of In Utero Programs on Birth Outcomes: The Case of <em>Buen
Comienzo</em>
Authors: Cardona-Sosa Lina , Medina Carlos 
Published: March 2023

This paper studies the effects of an in utero program on birth outcomes for
vulnerable pregnant women. We use information from the Buen Comienzo program, an
initiative run by the local government of Medellín, the second-largest city of Colombia.
To identify the effects, we obtain matching estimates using data from program
participants and national birth statistics. We find that the program increased the birth
weight of participant children by 0.09 and 0.23 standard deviations for boys and girls,
respectively, and reduced the prevalence of low birth weight by 2.6 and 4.6 percentage
points for boys and girls, respectively. In terms of size, the program reduces the
incidence of being short by 3 and 4 percentage points, for boys and girls, respectively.
The program also significantly reduced preterm births between 3 and 8 percentage points.
We also provide evidence of the existence of heterogeneous effects depending on a
mother’s exposure to the program and her frequency of attendance. Finally, an estimate
of the cost-benefit ratio of the program suggests that the benefits could be two to six
times the costs, respectively, for boys and girls born to participant mothers with early
exposure to the program. JEL Classifications: I38, J13, J18